Detection kit or device and detection method for prostate cancer
By developing detection kits and methods containing multiple miRNA markers, the problems of high false positive rates and low sensitivity in PSA examinations have been solved, which significantly improves the detection accuracy and reliability of prostate cancer and provides more effective diagnostic tools .
Patent Information
- Application Number
- CN202411379412.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2015-03-31
- Filing Date
- 2015-06-12
- Publication Date
- 2024-12-31
AI Technical Summary
Among the existing detection methods for prostate cancer, PSA examination has a high false positive rate and low sensitivity, which leads to overdiagnosis and overtreatment. The detection of microRNA (miRNA) has not been practical, and the reliability and effectiveness of existing miRNA markers are Sex is not fully proven.
A detection kit and method containing multiple miRNA markers was developed to collect markers from the blood in a low-invasive manner through specifically bound nucleic acids for the detection of prostate cancer, including miR-4443, miR-1908- 5p, miR-4257 and other miRNAs improve the sensitivity and specificity of detection.
It significantly improves the detection accuracy and reliability of prostate cancer, reduces the false positive rate, provides more effective diagnostic tools, and reduces unnecessary treatments.
Smart Images

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Abstract
Description
[0001] This application is a divisional application of a patent application filed on June 12, 2015, with application number 202010727753.8 and invention name “Prostate cancer detection kit or device and detection method”. Technical Field
[0002] The present invention relates to a prostate cancer detection kit or device for examining whether a subject has prostate cancer, comprising a nucleic acid capable of specifically binding to a specific miRNA, and a prostate cancer detection method comprising using the nucleic acid to measure the expression level of the miRNA. Background Art
[0003] The prostate is an organ that produces part of male semen and is located below the bladder and in front of the rectum. Prostate cancer is a disease in which the cells of the prostate gland proliferate repeatedly and disorderly. According to the statistics of cancers of various parts of the body in Japan in 2011 disclosed by the Cancer Countermeasures Information Center of the National Cancer Research Center, an independent administrative agency, the number of patients with prostate cancer is 51,534 people, that is, it is believed that 1 in 14 male Japanese people suffers from it, making it the fourth most common cancer site among men. In addition, the number of deaths caused by prostate cancer has risen to 10,823 people, making it the sixth most common cancer site among men. In addition, it is said that in the United States, men develop prostate cancer at a ratio of 1 in 7, and it is more common among the elderly. When they are over 65 years old, 6 in 10 men are diagnosed with prostate cancer (non-patent literature 1). The estimated number of patients with prostate cancer in the United States in 2014 also rose to 233,000 people, of which about 29,480 are believed to have died (non-patent literature 1).
[0004] The progression of prostate cancer is defined in non-patent document 2 and is classified into stage I (T1-T2a / N0 / M0), stage II (T2b-c / N0 / M0), stage III (T3 / N0 / M0), and stage IV (T4 / N0 / M0 and N1 and cM1) based on tumor spread (T1a-c, T2a-c, T3a-b, T4), lymph node metastasis (N0, N1), and distant metastasis (M0, M1a-c).
[0005] Most prostate cancers progress relatively slowly, resulting in a 5-year relative survival rate of approximately 100%, making it one of the cancers with the best prognosis (Non-Patent Document 1). However, prostate cancers progress relatively early, sometimes causing various disorders and symptoms, and the 5-year relative survival rate for prostate cancers with confirmed stage 4 distant metastasis is remarkably low, at 28% (Non-Patent Document 1).
[0006] In principle, prostate cancer treatments include surgery, radiotherapy, and endocrine therapy (hormone therapy). Furthermore, watchful waiting is a method of continuous observation while monitoring PSA, a tumor marker, without any specific treatment. In particular, early-stage prostate cancer treatment options include external beam radiation therapy, internal radiation therapy (short-course therapy), radical prostatectomy, and cryosurgery (Non-Patent Document 1).
[0007] As described in Non-Patent Document 1, PSA testing, a blood tumor marker, is widely used in primary prostate cancer screening. If the PSA value is high, a rectal examination and transrectal prostate ultrasound examination are performed. Furthermore, if prostate cancer is suspected, a tissue examination is performed to confirm the diagnosis. Furthermore, if distant metastasis is suspected, imaging tests such as CT scans, MRI scans, and bone scintigraphy are also performed.
[0008] PSA, a prostate-specific antigen, is produced by the prostate and contained in semen, but only exists in a small amount in the blood. It is believed that the normal blood PSA concentration of an average man is below 4 ng / mL. When this baseline value is exceeded, prostate cancer is suspected (non-patent document 1). The blood PSA concentration rises even in the early stage of prostate cancer without symptoms, and is also related to the progression of cancer. Therefore, it is considered to be useful and widely popularized. In addition, the American Cancer Society recommends early detection of prostate cancer and suggests that subjects who wish to be screened for prostate cancer should undergo PSA examination (non-patent document 1).
[0009] Although still in the research stage, as shown in Patent Documents 1 to 3, there are reports of detecting prostate cancer by measuring the expression level of microRNA (miRNA) in biological samples such as blood, or by combining the expression level of miRNA with the expression levels of other markers.
[0010] Patent document 1 shows the following method: a method for detecting prostate cancer, Wilms' tumor and COPD, represented by prostate cancer, as well as hsa-miR-760, hsa-miR-920, hsa-miR-887-3p, hsa-miR-486-3p, hsa-miR-663b, hsa-miR-187-5p, hsa-miR-1231, hsa-miR-371a-5p, hsa-miR-575, hsa-miR-615-5p, hsa-miR-711, hsa-miR-939-5p, hsa-miR-1203, hsa-miR-1225-3p, hsa-miR-1225-5p, hsa-miR-1915-5p and the like in the blood.
[0011] Patent Document 2 discloses a method for isolating vesicles in blood using EpCam and detecting prostate cancer and the like using miRNAs such as hsa-miR-92b-5p contained in the vesicles.
[0012] Patent Document 3 reports that prostate cancer can be identified by combining the expression level of the PCA3 gene with the expression level of miR-141.
[0013] Prior art literature
[0014] Patent Literature
[0015] Patent Document 1: European Patent Application Publication No. 2341145
[0016] Patent Document 2: International Publication No. 2013 / 022995
[0017] Patent Document 3: International Publication No. 2010 / 062706
[0018] Non-patent literature
[0019] Non-patent document 1: American Cancer Society "Prostate Cancer", 2013, pp. 5, 14-26, 32-54, 68-70
[0020] Non-patent document 2: Sobin, L. et al., "TNM Classification of Malignant Tumours 7th Edition," 2010, pp. 230-234
[0021] Non-patent document 3: Wolf, AM. et al., 2010, A Cancer Journal for Clinicians, Vol. 60(2), pp. 70-98
[0022] Non-patent document 4: Mitchell PS. et al., 2008, Proceedings of the National Academy of Sciences of the United States of America, Vol. 105(30), pp. 10513-10518 Summary of the Invention
[0023] Problems to be solved by the invention
[0024] The subject of the present invention is to find a new prostate cancer tumor marker and to provide a method for effectively detecting prostate cancer using a nucleic acid that can specifically bind to the marker. As a tumor marker test for prostate cancer, PSA testing has been widely popularized. However, it is known that in PSA testing, even in men with a blood concentration baseline of 4 ng / mL or less, 15% are judged to be positive for prostate cancer during biological tissue examination. On the other hand, it is also known that if a man has benign prostatic hyperplasia or prostatitis instead of cancer, as well as general elderly men, the false positive rate is high due to the increase in blood PSA concentration (non-patent document 1). In addition, the case of being misdiagnosed as a cancer other than prostate cancer and being tested is also related to false positives. Such high false positives in PSA tests are related to overdiagnosis and overtreatment, and various sequelae caused by unnecessary prostate cancer treatment have been regarded as problems in recent years (non-patent document 3). Regarding the specific performance of PSA testing, according to a large-scale study that recruited more than 5,000 subjects (non-patent document 3), the overall sensitivity for prostate cancer is as low as 20.5%, and even for highly malignant prostate cancer, it is limited to 51%. It is believed that there is no significance in measuring tumor markers as a preoperative examination.
[0025] Furthermore, although still in the research stage, there are reports such as the following that use the expression levels of microRNA (miRNA) in biological samples such as blood to discriminate prostate cancer, but none of them has been put into practical use.
[0026] Patent document 1 shows a method for detecting prostate cancer, nephroblastoma, and COPD using hsa-miR-760, hsa-miR-920, hsa-miR-887-3p, hsa-miR-486-3p, hsa-miR-663b, hsa-miR-187-5p, hsa-miR-1231, hsa-miR-371a-5p, hsa-miR-575, hsa-miR-615-5p, hsa-miR-711, hsa-miR-939-5p, hsa-miR-1203, hsa-miR-1225-3p, hsa-miR-1225-5p, hsa-miR-1915-5p, etc. in the blood. However, Patent Document 1 describes a large number of miRNAs, but does not directly describe that the miRNA markers are prostate cancer markers, and lacks proof of the usefulness of the miRNA markers as prostate cancer markers.
[0027] Patent document 2 shows a method of using EpCam to separate vesicles in the blood and using miRNAs such as hsa-miR-92b-5p contained in the vesicles to detect prostate cancer. However, the above-mentioned miRNA markers have not been reproduced and verified by an independent specimen group, and the criteria for detecting prostate cancer are not recorded, so they lack reliability.
[0028] Specifically, Patent Document 3 states that by combining the expression levels of miR-141 and PCA3, prostate cancer can be identified with a sensitivity and specificity of 100%, but there is no record of such identification being possible using a single marker in a simple and highly accurate manner. In fact, Patent Document 3 cites Non-Patent Document 4, which reports the use of miR-141 in serum for prostate cancer identification, and believes that the accuracy of the identification is 60% when the specificity is 100%. In addition, the object specimen for PCA3 examination currently used is urine, in particular, urine after digital rectal examination. On the other hand, the object specimen for prostate cancer identification using miR-141 is blood (serum) as mentioned above, and combining the two to obtain a result with high sensitivity and specificity requires the collection of two specimens.
[0029] Means for solving problems
[0030] The present inventors conducted in-depth research to solve the above-mentioned problems and found that by finding multiple genes that can be used as detection markers for prostate cancer from blood that can be collected with low invasiveness and using nucleic acids that can specifically bind to them, prostate cancer can be significantly detected, thus completing the present invention.
[0031] <Summary of the Invention>
[0032] That is, the present invention has the following features.
[0033] (1) A kit for the detection of prostate cancer, which comprises agents capable of binding to miR-4443, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4258, miR-4448, miR-6125, miR-6880-5p, miR-6132, miR-4467, miR-6749-5p, miR-2392, miR-1273g-3p, miR-47th46-3p, miR-1914-3p, miR-7845-5p, miR-6726-5p, miR-128-2-5p, miR-4651, miR-6765-3p, miR-3185, miR-4792, miR-6887-5p, miR-5572, miR-3619-3p, miR-6870b-5p, miR-4707-5p, miR-8063, miR-4454, miR-4525, miR-7975, miR-744-5p, miR-3135b, miR-4648, miR-6816-5p, miR-4741, miR-7150, miR-6791-5p, miR-1247-3p, miR-7977, miR-4497, miR-6090, miR-6781-5p, miR-6870-5p, miR-6729-5p, miR-4530, miR-7847-3p, miR-6825-5p, miR-4674, miR-3917, miR-4707-3p, miR-6885-5p, miR-6722-3p, miR-4516, miR-67th57-5p, miR-6840-3p, miR-5195-3p, miR-6756-5p, miR-6800-5p, miR-6727-5p, miR-6126, miR-6872-3p, miR-4446-3p, miR-1268a, miR-th1908-3p, miR-3679-5p, miR-4534, miR-4675, miR-7108-5p, miR-6799-5p, miR-4695-5p, miR-3178, miR-5090, miR-3180, miR-1237-5p, miR-4758-5p, miR-3184-5p, which are selected as prostate cancer markers. It should be noted that there may be some inaccuracies in the original text (such as "miR-47th46-3p", "miR-6870b-5p", "miR-67th57-5p", "miR-1908-3p", etc. which seem to have incorrect notations). The translation is based on the existing text as accurately as possible.A nucleic acid that specifically binds to at least one polynucleotide among miR-4286, miR-6784-5p, miR-6768-5p, miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5p, miR-4689, miR-6763-5p, miR-8072, miR-6765-5p, miR-4419b, miR-7641, miR-3928-3p, miR-1227-5p, miR-4492, miR-296-3p, miR-6769a-5p, miR-6889-5p, miR-4632-5p, miR-4505, miR-3154, miR-3648, miR-4442, miR-3141, miR-7113-3p, miR-6819-5p, miR-3195, miR-1199-5p, miR-6738-5p, miR-4656, miR-6820-5p, miR-204-3p, miR-642a-3p, miR-762, miR-1202, miR-3162-5p, miR-3196, miR-3622a-5p, miR-3665, miR-3940-5p, miR-4294, miR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p, and miR-6893-5p.
[0034] (2) The kit according to (1), wherein miR-4443 is hsa-miR-4443, miR-1908-5p is hsa-miR-1908-5p, miR-4257 is hsa-miR-4257, miR-3197 is hsa-miR-3197, miR-3188 is hsa-miR-3188, miR-4649-5p is hsa-miR-4649-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6861-5p is hsa-miR-6861-5p, miR-1343-5p is hsa-miR-1343-5p, and miR- 642b-3p is hsa-miR-642b-3p, miR-6741-5p is hsa-miR-6741-5p, miR-4745-5p is hsa-miR-4745-5p, miR-6826-5p is hsa-miR-6826-5p, miR-3663-3p is hsa-miR-3663-3p, miR-3131 is hsa-miR-3131, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4258 is hsa-miR-4258, miR-4448 is hsa-miR-4448, and miR-6125 is hsa-miR-6126. 125, miR-6880-5p was hsa-miR-6880-5p, miR-6132 was hsa-miR-6132, miR-4467 was hsa-miR-4467, miR-6749-5p was hsa-miR-6749-5p, miR-2392 was hsa-miR-2392, miR-1273g-3p was hsa-miR-1273g-3p, miR-4746-3p was hsa-miR-4746-3p, miR-1914-3p was hsa-miR-1914-3p, miR-7845-5p was hsa-miR-7845-5p, miR-6726-5 p is hsa-miR-6726-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4651 is hsa-miR-4651, miR-6765-3p is hsa-miR-6765-3p, miR-3185 is hsa-miR-3185, miR-4792 is hsa-miR-4792, miR-6887-5p is hsa-miR-6887-5p, miR-5572 is hsa-miR-5572, miR-3619-3p is hsa-miR-3619-3p, miR-6780b-5p is hsa-miR-6780b-5p,miR-4707-5p is hsa-miR-4707-5p, miR-8063 is hsa-miR-8063, miR-4454 is hsa-miR-4454, miR-4525 is hsa-miR-4525, miR-7975 is hsa-miR-7975, miR-744-5p is hsa-miR-744-5p, miR-3135b is hsa-miR-3135b, miR-4648 is hsa-miR-4648, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa-miR-4741, and miR-7150 is hsa-miR-7151. sa-miR-7150, miR-6791-5p is hsa-miR-6791-5p, miR-1247-3p is hsa-miR-1247-3p, miR-7977 is hsa-miR-7977, miR-4497 is hsa-miR-4497, miR-6090 is hsa-miR-6090, miR-6781-5p is hsa-miR-6781-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4530 is hsa-miR-4530, miR-7847 is hsa-miR-7150 -3p is hsa-miR-7847-3p, miR-6825-5p is hsa-miR-6825-5p, miR-4674 is hsa-miR-4674, miR-3917 is hsa-miR-3917, miR-4707-3p is hsa-miR-4707-3p, miR-6885-5p is hsa-miR-6885-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4516 is hsa-miR-4516, miR-6757-5p is hsa-miR-6757-5p, and miR-6840-3p is hsa-miR-6840-3p. 40-3p, miR-5195-3p is hsa-miR-5195-3p, miR-6756-5p is hsa-miR-6756-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6727-5p is hsa-miR-6727-5p, miR-6126 is hsa-miR-6126, miR-6872-3p is hsa-miR-6872-3p, miR-4446-3p is hsa-miR-4446-3p, miR-1268a is hsa-miR-1268a, miR-1908-3p is hsa-miR-1908-3p,miR-3679-5p is hsa-miR-3679-5p, miR-4534 is hsa-miR-4534, miR-4675 is hsa-miR-4675, miR-7108-5p is hsa-miR-7108-5p, miR-6799-5p is hsa-miR-6799-5p, miR-4695-5p is hsa-miR-4695-5p, miR-3178 is hsa-miR-3178, miR-5090 is hsa-miR-5090, miR-3180 is hsa-miR-3180, and miR-1237-5p is hsa-miR-1237-5p. 37-5p, miR-4758-5p is hsa-miR-4758-5p, miR-3184-5p is hsa-miR-3184-5p, miR-4286 is hsa-miR-4286, miR-6784-5p is hsa-miR-6784-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6785-5p is hsa-miR-6785-5p, miR-4706 is hsa-miR-4706, miR-711 is hsa-miR-711, miR-1260a is hsa-miR-1260a, miR-6746-5 p is hsa-miR-6746-5p, miR-6089 is hsa-miR-6089, miR-6821-5p is hsa-miR-6821-5p, miR-4667-5p is hsa-miR-4667-5p, miR-8069 is hsa-miR-8069, miR-4726-5p is hsa-miR-4726-5p, miR-6124 is hsa-miR-6124, miR-4532 is hsa-miR-4532, miR-4486 is hsa-miR-4486, miR-4728-5p is hsa-miR-4728-5p, miR- 4508 is hsa-miR-4508, miR-128-1-5p is hsa-miR-128-1-5p, miR-4513 is hsa-miR-4513, miR-6795-5p is hsa-miR-6795-5p, miR-4689 is hsa-miR-4689, miR-6763-5p is hsa-miR-6763-5p, miR-8072 is hsa-miR-8072, miR-6765-5p is hsa-miR-6765-5p, miR-4419b is hsa-miR-4419b, miR-7641 is hsa-miR-7641,miR-3928-3p is hsa-miR-3928-3p, miR-1227-5p is hsa-miR-1227-5p, miR-4492 is hsa-miR-4492, miR-296-3p is hsa-miR-296-3p, miR-6769a-5p is hsa-miR-6769a-5p, miR-6889-5p is hsa-miR-6889-5p, miR-4632-5p is hsa-miR-4632-5p, miR-4505 is hsa-miR-4505, miR-3154 is hsa-miR-3154, and miR-3648 is hsa-miR-3649. sa-miR-3648, miR-4442 is hsa-miR-4442, miR-3141 is hsa-miR-3141, miR-7113-3p is hsa-miR-7113-3p, miR-6819-5p is hsa-miR-6819-5p, miR-3195 is hsa-miR-3195, miR-1199-5p is hsa-miR-1199-5p, miR-6738-5p is hsa-miR-6738-5p, miR-4656 is hsa-miR-4656, miR-6820-5p is hsa-miR-6820-5p, miR- 204-3p is hsa-miR-204-3p, miR-642a-3p is hsa-miR-642a-3p, miR-762 is hsa-miR-762, miR-1202 is hsa-miR-1202, miR-3162-5p is hsa-miR-3162-5p, miR-3196 is hsa-miR-3196, miR-3622a-5p is hsa-miR-3622a-5p, miR-3665 is hsa-miR-3665, miR-3940-5p is hsa-miR-3940-5p, miR-4294 is hsa-miR-4294, miR-4466 is hsa-miR-4466, miR-4476 is hsa-miR-4476, miR-4723-5p is hsa-miR-4723-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4730 is hsa-miR-4730, miR-4739 is hsa-miR-4739, miR-4787-5p is hsa-miR-4787-5p, miR-5787 is hsa-miR-5787, miR-6085 is hsa-miR-6085, miR-6717-5p is hsa-miR-6717-5p,miR-6724-5p is hsa-miR-6724-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6778-5p is hsa-miR-6778-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6845-5p is hsa-miR-6845-5p, and miR-6893-5p is hsa-miR-6893-5p. ,
[0035] (3) The kit according to (1) or (2), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a) to (e),
[0036] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0037] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606,
[0038] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0039] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, and
[0040] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0041] (4) The kit according to any one of (1) to (3), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, miR-575, miR-92b-5p, miR-887-3p, miR-920, miR-1915-5p, miR-1231, miR-663b, miR-1225-5p, miR-16-5p, miR-423-5p, miR-451a, miR-564 and miR-671-5p, which are other prostate cancer markers.
[0042] (5) The kit according to (4), wherein miR-615-5p is hsa-miR-615-5p, miR-486-3p is hsa-miR-486-3p, miR-1225-3p is hsa-miR-1225-3p, miR-760 is hsa-miR-760, miR-187-5p is hsa-miR-187-5p, miR-1203 is hsa-miR-1203, miR-7110-5p is hsa-miR-7110-5p, miR-371a-5p is hsa-miR-371a-5p, miR-939-5p is hsa-miR-939-5p, miR-575 is hsa-miR-575, and miR-92b-5p is hsa-miR-575. hsa-miR-92b-5p, miR-887-3p was hsa-miR-887-3p, miR-920 was hsa-miR-920, miR-1915-5p was hsa-miR-1915-5p, miR-1231 was hsa-miR-1231, miR-663b was hsa-miR-663b, miR-1225-5p was hsa-miR-1225-5p, miR-16-5p was hsa-miR-16-5p, miR-423-5p was hsa-miR-423-5p, miR-451a was hsa-miR-451a, miR-564 was hsa-miR-564 and miR-671-5p was hsa-miR-671-5p.
[0043] (6) The kit according to (4) or (5), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (j),
[0044] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in such a base sequence, a variant of such a polynucleotide, a derivative of such a polynucleotide, or a fragment of such a polynucleotide comprising 15 or more consecutive bases,
[0045] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 136 to 152, and 607 to 611,
[0046] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0047] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 136 to 152, and 607 to 611, or a base sequence in which u is t in the base sequence, and
[0048] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0049] (7) The kit according to any one of (1) to (6), further comprising a protein capable of interacting with other prostate cancer markers selected from the group consisting of miR-4763-3p, miR-3656, miR-4488, miR-125a-3p, miR-1469, miR-1228-5p, miR-6798-5p, miR-1268b, miR-6732-5p, miR-1915-3p, miR-4433b-3p, miR-1207-5p, miR-4433-3p, miR-6879-5p, miR-4417, miR-30c- A nucleic acid that specifically binds to at least one of the polynucleotides selected from the group consisting of miR-1-3p, miR-4638-5p, miR-6088, miR-4270, miR-6782-5p, miR-665, miR-486-5p, miR-4655-5p, miR-1275, miR-6806-5p, miR-614, miR-3937, miR-6752-5p, miR-6771-5p, miR-4450, miR-211-3p, miR-663a, miR-6842-5p, miR-7114-5p, and miR-6779-5p.
[0050] (8) The kit according to (7), wherein miR-4763-3p is hsa-miR-4763-3p, miR-3656 is hsa-miR-3656, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-1469 is hsa-miR-1469, miR-1228-5p is hsa-miR-1228-5p, miR-6798-5p is hsa-miR-6798-5p, miR-1268b is hsa-miR-1268b, and miR-6732-5p is hsa-miR-6732-5p. p is hsa-miR-6732-5p, miR-1915-3p is hsa-miR-1915-3p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1207-5p is hsa-miR-1207-5p, miR-4433-3p is hsa-miR-4433-3p, miR-6879-5p is hsa-miR-6879-5p, miR-4417 is hsa-miR-4417, miR-30c-1-3p is hsa-miR-30c-1-3p, and miR-4638-5p is hsa-miR-4639-5p. iR-4638-5p, miR-6088 is hsa-miR-6088, miR-4270 is hsa-miR-4270, miR-6782-5p is hsa-miR-6782-5p, miR-665 is hsa-miR-665, miR-486-5p is hsa-miR-486-5p, miR-4655-5p is hsa-miR-4655-5p, miR-1275 is hsa-miR-1275, miR-6806-5p is hsa-miR-6806-5p, miR-614 is hsa-miR-614, miR- R-3937 is hsa-miR-3937, miR-6752-5p is hsa-miR-6752-5p, miR-6771-5p is hsa-miR-6771-5p, miR-4450 is hsa-miR-4450, miR-211-3p is hsa-miR-211-3p, miR-663a is hsa-miR-663a, miR-6842-5p is hsa-miR-6842-5p, miR-7114-5p is hsa-miR-7114-5p, and miR-6779-5p is hsa-miR-6779-5p.
[0051] (9) The kit according to (7) or (8), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (k) to (o),
[0052] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0053] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 153 to 187,
[0054] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0055] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, and
[0056] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0057] (10) The kit according to any one of (1) to (9), comprising at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides selected from all the prostate cancer markers described in (1) or (2).
[0058] (11) Device for detecting prostate cancer, comprising a substance that can bind to a prostate cancer marker selected from miR-4443, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4258, miR-4448, miR-6125, miR-6880-5p, miR-6132, miR-4467, miR-6749-5p, miR-2392, miR-1273g-3p, miR-4746-3p, miR-1914-3p, miR-7845-5p, miR-6726-5p, miR-128-2-5p, miR-4651, miR-6765-3p, miR-3185, miR-4792, miR-6887-5p, miR-5572, miR-3619-3p, miR-6780b-5p, miR-4707-5p, miR-8063, miR-4454, miR-4525, miR-7975, miR-744-5p, miR-3135b, miR-4648, miR-6816-5p, miR-4741, miR-7150, miR-6791-5p, miR-1247-3p, miR-7977, miR-4497, miR-6090, miR-6781-5p, miR-6870-5p, miR-6729-5p, miR-4530, miR-7847-3p, miR-6825-5p, miR-4674, miR-3917, miR-4707-3p, miR-6885-5p, miR-6722-3p, miR-4516, miR-6757-5p, miR-6840-3p, miR-5195-3p, miR-6756-5p, miR-6800-5p, miR-6727-5p, miR-6126, miR-6872-3p, miR-4446-3p, miR-1268a, miR-1908-3p, miR-3679-5p, miR-4534, miR-4675, miR-7108-5p, miR-6799-5p, miR-4695-5p, miR-3178, miR-5090, miR-3180, miR-1237-5p, miR-4758-5p, miR-3184-5p,A nucleic acid that specifically binds to at least one polynucleotide selected from miR-4286, miR-6784-5p, miR-6768-5p, miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5p, miR-4689, miR-6763-5p, miR-8072, miR-6765-5p, miR-4419b, miR-7641, miR-3928-3p, miR-1227-5p, miR-4492, miR-296-3p, miR-6769a-5p, miR-6889-5p, miR-4632-5p, miR-4505, miR-3154, miR-3648, miR-4442, miR-3141, miR-7113-3p, miR-6819-5p, miR-3195, miR-1199-5p, miR-6738-5p, miR-4656, miR-6820-5p, miR-204-3p, miR-642a-3p, miR-762, miR-1202, miR-3162-5p, miR-3196, miR-3622a-5p, miR-3665, miR-3940-5p, miR-4294, miR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p, and miR-6893-5p.
[0059] (12) The device according to (11), wherein miR-4443 is hsa-miR-4443, miR-1908-5p is hsa-miR-1908-5p, miR-4257 is hsa-miR-4257, miR-3197 is hsa-miR-3197, miR-3188 is hsa-miR-3188, miR-4649-5p is hsa-miR-4649-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6861-5p is hsa-miR-6861-5p, miR-1343-5p is hsa-miR-1343-5p, and miR- 642b-3p is hsa-miR-642b-3p, miR-6741-5p is hsa-miR-6741-5p, miR-4745-5p is hsa-miR-4745-5p, miR-6826-5p is hsa-miR-6826-5p, miR-3663-3p is hsa-miR-3663-3p, miR-3131 is hsa-miR-3131, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4258 is hsa-miR-4258, miR-4448 is hsa-miR-4448, and miR-6125 is hsa-miR-6126. 125, miR-6880-5p was hsa-miR-6880-5p, miR-6132 was hsa-miR-6132, miR-4467 was hsa-miR-4467, miR-6749-5p was hsa-miR-6749-5p, miR-2392 was hsa-miR-2392, miR-1273g-3p was hsa-miR-1273g-3p, miR-4746-3p was hsa-miR-4746-3p, miR-1914-3p was hsa-miR-1914-3p, miR-7845-5p was hsa-miR-7845-5p, miR-6726-5 p is hsa-miR-6726-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4651 is hsa-miR-4651, miR-6765-3p is hsa-miR-6765-3p, miR-3185 is hsa-miR-3185, miR-4792 is hsa-miR-4792, miR-6887-5p is hsa-miR-6887-5p, miR-5572 is hsa-miR-5572, miR-3619-3p is hsa-miR-3619-3p, miR-6780b-5p is hsa-miR-6780b-5p,miR-4707-5p is hsa-miR-4707-5p, miR-8063 is hsa-miR-8063, miR-4454 is hsa-miR-4454, miR-4525 is hsa-miR-4525, miR-7975 is hsa-miR-7975, miR-744-5p is hsa-miR-744-5p, miR-3135b is hsa-miR-3135b, miR-4648 is hsa-miR-4648, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa-miR-4741, and miR-7150 is hsa-miR-7151. sa-miR-7150, miR-6791-5p is hsa-miR-6791-5p, miR-1247-3p is hsa-miR-1247-3p, miR-7977 is hsa-miR-7977, miR-4497 is hsa-miR-4497, miR-6090 is hsa-miR-6090, miR-6781-5p is hsa-miR-6781-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4530 is hsa-miR-4530, miR-7847 is hsa-miR-7150 -3p is hsa-miR-7847-3p, miR-6825-5p is hsa-miR-6825-5p, miR-4674 is hsa-miR-4674, miR-3917 is hsa-miR-3917, miR-4707-3p is hsa-miR-4707-3p, miR-6885-5p is hsa-miR-6885-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4516 is hsa-miR-4516, miR-6757-5p is hsa-miR-6757-5p, and miR-6840-3p is hsa-miR-6840-3p. 40-3p, miR-5195-3p is hsa-miR-5195-3p, miR-6756-5p is hsa-miR-6756-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6727-5p is hsa-miR-6727-5p, miR-6126 is hsa-miR-6126, miR-6872-3p is hsa-miR-6872-3p, miR-4446-3p is hsa-miR-4446-3p, miR-1268a is hsa-miR-1268a, miR-1908-3p is hsa-miR-1908-3p,miR-3679-5p is hsa-miR-3679-5p, miR-4534 is hsa-miR-4534, miR-4675 is hsa-miR-4675, miR-7108-5p is hsa-miR-7108-5p, miR-6799-5p is hsa-miR-6799-5p, miR-4695-5p is hsa-miR-4695-5p, miR-3178 is hsa-miR-3178, miR-5090 is hsa-miR-5090, miR-3180 is hsa-miR-3180, and miR-1237-5p is hsa-miR-1237-5p. 37-5p, miR-4758-5p is hsa-miR-4758-5p, miR-3184-5p is hsa-miR-3184-5p, miR-4286 is hsa-miR-4286, miR-6784-5p is hsa-miR-6784-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6785-5p is hsa-miR-6785-5p, miR-4706 is hsa-miR-4706, miR-711 is hsa-miR-711, miR-1260a is hsa-miR-1260a, miR-6746-5 p is hsa-miR-6746-5p, miR-6089 is hsa-miR-6089, miR-6821-5p is hsa-miR-6821-5p, miR-4667-5p is hsa-miR-4667-5p, miR-8069 is hsa-miR-8069, miR-4726-5p is hsa-miR-4726-5p, miR-6124 is hsa-miR-6124, miR-4532 is hsa-miR-4532, miR-4486 is hsa-miR-4486, miR-4728-5p is hsa-miR-4728-5p, miR- 4508 is hsa-miR-4508, miR-128-1-5p is hsa-miR-128-1-5p, miR-4513 is hsa-miR-4513, miR-6795-5p is hsa-miR-6795-5p, miR-4689 is hsa-miR-4689, miR-6763-5p is hsa-miR-6763-5p, miR-8072 is hsa-miR-8072, miR-6765-5p is hsa-miR-6765-5p, miR-4419b is hsa-miR-4419b, miR-7641 is hsa-miR-7641,miR-3928-3p is hsa-miR-3928-3p, miR-1227-5p is hsa-miR-1227-5p, miR-4492 is hsa-miR-4492, miR-296-3p is hsa-miR-296-3p, miR-6769a-5p is hsa-miR-6769a-5p, miR-6889-5p is hsa-miR-6889-5p, miR-4632-5p is hsa-miR-4632-5p, miR-4505 is hsa-miR-4505, miR-3154 is hsa-miR-3154, and miR-3648 is hsa-miR-3649. sa-miR-3648, miR-4442 is hsa-miR-4442, miR-3141 is hsa-miR-3141, miR-7113-3p is hsa-miR-7113-3p, miR-6819-5p is hsa-miR-6819-5p, miR-3195 is hsa-miR-3195, miR-1199-5p is hsa-miR-1199-5p, miR-6738-5p is hsa-miR-6738-5p, miR-4656 is hsa-miR-4656, miR-6820-5p is hsa-miR-6820-5p, miR- 204-3p is hsa-miR-204-3p, miR-642a-3p is hsa-miR-642a-3p, miR-762 is hsa-miR-762, miR-1202 is hsa-miR-1202, miR-3162-5p is hsa-miR-3162-5p, miR-3196 is hsa-miR-3196, miR-3622a-5p is hsa-miR-3622a-5p, miR-3665 is hsa-miR-3665, miR-3940-5p is hsa-miR-3940-5p, miR-4294 is hsa-miR-4294, miR-4466 is hsa-miR-4466, miR-4476 is hsa-miR-4476, miR-4723-5p is hsa-miR-4723-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4730 is hsa-miR-4730, miR-4739 is hsa-miR-4739, miR-4787-5p is hsa-miR-4787-5p, miR-5787 is hsa-miR-5787, miR-6085 is hsa-miR-6085, miR-6717-5p is hsa-miR-6717-5p,miR-6724-5p is hsa-miR-6724-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6778-5p is hsa-miR-6778-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6845-5p is hsa-miR-6845-5p, and miR-6893-5p is hsa-miR-6893-5p. ,
[0060] (13) The device according to (11) or (12), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in (a) to (e) below,
[0061] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0062] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606,
[0063] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0064] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, and
[0065] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0066] (14) The device according to any one of (11) to (13), further comprising a protein capable of interacting with other prostate cancer markers selected from miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, A nucleic acid that specifically binds to at least one polynucleotide selected from the group consisting of miR-575, miR-92b-5p, miR-887-3p, miR-920, miR-1915-5p, miR-1231, miR-663b, miR-1225-5p, miR-16-5p, miR-423-5p, miR-451a, miR-564, and miR-671-5p.
[0067] (15) The device according to (14), wherein miR-615-5p is hsa-miR-615-5p, miR-486-3p is hsa-miR-486-3p, miR-1225-3p is hsa-miR-1225-3p, miR-760 is hsa-miR-760, miR-187-5p is hsa-miR-187-5p, miR-1203 is hsa-miR-1203, miR-7110-5p is hsa-miR-7110-5p, miR-371a-5p is hsa-miR-371a-5p, miR-939-5p is hsa-miR-939-5p, miR-575 is hsa-miR-575, and miR-92b-5p is hsa-miR-92b-5p. hsa-miR-92b-5p, miR-887-3p was hsa-miR-887-3p, miR-920 was hsa-miR-920, miR-1915-5p was hsa-miR-1915-5p, miR-1231 was hsa-miR-1231, miR-663b was hsa-miR-663b, miR-1225-5p was hsa-miR-1225-5p, miR-16-5p was hsa-miR-16-5p, miR-423-5p was hsa-miR-423-5p, miR-451a was hsa-miR-451a, miR-564 was hsa-miR-564 and miR-671-5p was hsa-miR-671-5p.
[0068] (16) The device according to (14) or (15), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (j),
[0069] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in such a base sequence, a variant of such a polynucleotide, a derivative of such a polynucleotide, or a fragment of such a polynucleotide comprising 15 or more consecutive bases,
[0070] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 136 to 152, and 607 to 611,
[0071] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0072] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 136 to 152, and 607 to 611, or a base sequence in which u is t in the base sequence, and
[0073] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0074] (17) The device according to any one of (11) to (16), further comprising a device capable of interacting with other prostate cancer markers selected from miR-4763-3p, miR-3656, miR-4488, miR-125a-3p, miR-1469, miR-1228-5p, miR-6798-5p, miR-1268b, miR-6732-5p, miR-1915-3p, miR-4433b-3p, miR-1207-5p, miR-4433-3p, miR-6879-5p, miR-4417, miR-30c -1-3p, miR-4638-5p, miR-6088, miR-4270, miR-6782-5p, miR-665, miR-486-5p, miR-4655-5p, miR-1275, miR-6806-5p, miR-614, miR-3937, miR-6752-5p, miR-6771-5p, miR-4450, miR-211-3p, miR-663a, miR-6842-5p, miR-7114-5p and miR-6779-5p.
[0075] (18) The device according to (17), wherein miR-4763-3p is hsa-miR-4763-3p, miR-3656 is hsa-miR-3656, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-1469 is hsa-miR-1469, miR-1228-5p is hsa-miR-1228-5p, miR-6798-5p is hsa-miR-6798-5p, miR-1268b is hsa-miR-1268b, and miR-6732- 5p is hsa-miR-6732-5p, miR-1915-3p is hsa-miR-1915-3p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1207-5p is hsa-miR-1207-5p, miR-4433-3p is hsa-miR-4433-3p, miR-6879-5p is hsa-miR-6879-5p, miR-4417 is hsa-miR-4417, miR-30c-1-3p is hsa-miR-30c-1-3p, and miR-4638-5p is hsa-miR-4639-5p. iR-4638-5p, miR-6088 is hsa-miR-6088, miR-4270 is hsa-miR-4270, miR-6782-5p is hsa-miR-6782-5p, miR-665 is hsa-miR-665, miR-486-5p is hsa-miR-486-5p, miR-4655-5p is hsa-miR-4655-5p, miR-1275 is hsa-miR-1275, miR-6806-5p is hsa-miR-6806-5p, miR-614 is hsa-miR-614, miR- R-3937 is hsa-miR-3937, miR-6752-5p is hsa-miR-6752-5p, miR-6771-5p is hsa-miR-6771-5p, miR-4450 is hsa-miR-4450, miR-211-3p is hsa-miR-211-3p, miR-663a is hsa-miR-663a, miR-6842-5p is hsa-miR-6842-5p, miR-7114-5p is hsa-miR-7114-5p, and miR-6779-5p is hsa-miR-6779-5p.
[0076] (19) The device according to (17) or (18), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (k) to (o),
[0077] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0078] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 153 to 187,
[0079] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0080] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, and
[0081] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0082] (20) The device according to any one of (11) to (19), which is a device for performing measurements using hybridization technology.
[0083] (21) According to the device described in (20), the above-mentioned hybridization technology is nucleic acid array technology.
[0084] (22) The device according to any one of (11) to (21), comprising at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides selected from all prostate cancer markers described in (11) or (12).
[0085] (23) A method for detecting prostate cancer, comprising: using the kit described in any one of (1) to (10) or the device described in any one of (11) to (22) to determine the expression level of the target nucleic acid in a specimen of a subject, and using the measured expression level and a control expression level measured in a healthy subject in the same manner to perform in vitro evaluation of whether the subject has prostate cancer or not.
[0086] (24) According to the method described in (23), the subject is a human.
[0087] (25) The method according to (23) or (24), wherein the specimen is blood, serum or plasma.
[0088] Definition of Terms
[0089] The terms used in this specification have the following definitions.
[0090] Abbreviations such as nucleotide, polynucleotide, DNA, RNA, etc. are represented in accordance with the "Guidelines for the Preparation of Specifications, etc. Containing Base Sequences or Amino Acid Sequences" (compiled by the Japan Patent Office) and common practice in this technical field.
[0091] In this specification, the term "polynucleotide" is used for nucleic acids including any one of RNA, DNA, and RNA / DNA (chimera). Additionally, the above DNA includes any one of cDNA, genomic DNA, and synthetic DNA. Furthermore, the above RNA includes any one of total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. In this specification, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced based on a specified base sequence (which can be either a natural or non-natural sequence) using, for example, an automated nucleic acid synthesizer. The term "non-natural sequence" in this specification is intended to be used in a broad sense and includes sequences different from natural sequences, such as sequences containing one or more nucleotide substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), etc. Additionally, in this specification, polynucleotide and nucleic acid are used interchangeably.
[0092] In this specification, a "fragment" is a polynucleotide having a continuous partial base sequence of a polynucleotide, desirably having a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more.
[0093] In this specification, the term "gene" is intended to be used to include not only RNA and double-stranded DNA but also each single-stranded DNA such as the sense strand (or coding strand) or the complementary strand (or antisense strand) that constitutes them. Additionally, there is no particular limitation on its length.
[0094] Therefore, in this specification, "gene", unless otherwise specified, includes: double-stranded DNA comprising human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand) comprising cDNA having a sequence complementary to the positive strand, microRNA (miRNA), and any of their fragments, and their transcription products. In addition, the "gene" is not only the "gene" shown by a specific base sequence (or sequence number), but also includes RNA having the same biological function as the RNA encoded by them, such as "nucleic acids" encoding homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. As such "nucleic acids" encoding homologs, mutants or derivatives, specifically, "nucleic acids" having a base sequence that hybridizes with the base sequence shown in any one of SEQ ID NOs. 1 to 684, or a base sequence in which u is t in the base sequence, or their complementary sequences under the stringent conditions described below, can be cited. In addition, "gene" may include, for example, expression control regions, coding regions, exons or introns, regardless of the difference in functional regions. Furthermore, the "gene" may be contained in cells, released outside the cells and exist independently, or may be enclosed in small vesicles called exosomes.
[0095] As used herein, "exosomes" are small vesicles surrounded by a lipid bilayer secreted by cells. Exosomes originate from multivesicular endosomes and, when released into the extracellular environment, sometimes contain biological substances such as "genes" such as RNA and DNA, as well as proteins. Exosomes are known to be present in body fluids such as blood, serum, plasma, and lymph.
[0096] As used herein, "transcript" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a region upstream of the gene called the promoter, synthesizing RNA in a manner complementary to the base sequence of the DNA, with ribonucleotides attached to the 3' end. This RNA contains not only the gene itself but also the entire sequence from the transcription start point to the end of the poly A sequence, represented by expression control regions, coding regions, exons, or introns.
[0097] In addition, as used herein, "microRNA (miRNA)" is intended to be used as a 15-25 base non-coding RNA that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleavage enzyme with RNase III cleavage activity, and incorporated into a protein complex called RISC, thereby participating in the translational repression of mRNA, unless otherwise specified. Furthermore, the "miRNA" used herein includes not only "miRNAs" represented by specific base sequences (or sequence numbers), but also precursors (pre-miRNA, pri-miRNA) of such "miRNAs," miRNAs with equivalent biological functions, such as homologs (i.e., homologs or orthologs), mutants resulting from genetic polymorphisms, and derivatives. Specifically, examples of such precursors, homologs, mutants, or derivatives include "miRNAs" that can be identified by miRBase version 20 (http: / / www.mirbase.org / ) and that hybridize under stringent conditions described below to the complementary sequence of any of the specific base sequences represented by any of SEQ ID NOs. 1 to 684. In addition, the "miRNA" used in this specification can be a gene product of a miR gene, such a gene product comprising a mature miRNA (for example, a non-coding RNA of 15 to 25 bases or 19 to 25 bases involved in mRNA translation inhibition as described above) or a miRNA precursor (for example, a pre-miRNA or pri-miRNA as described above).
[0098] The term "probe" as used herein includes a polynucleotide used to specifically detect RNA produced by gene expression or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
[0099] The term "primer" as used herein includes a polynucleotide that specifically recognizes and amplifies RNA produced by gene expression or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
[0100] Here, a complementary polynucleotide (complementary strand, minus strand) refers to a polynucleotide that is complementary to the full-length sequence of a polynucleotide consisting of a base sequence defined by any of SEQ ID NOs: 1 to 684, or a base sequence in which u is t in such a base sequence, or a partial sequence thereof (herein referred to as the plus strand for convenience), based on base pair relationships such as A:T(U) and G:C. However, such a complementary strand is not limited to being completely complementary to the base sequence of the target plus strand and may also be complementary to the extent that it can hybridize with the target plus strand under stringent conditions.
[0101] As used herein, "stringent conditions" refer to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater degree (e.g., the mean of the background values + the standard error of the background values × 2 or greater) than to other sequences. Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization is performed. By controlling the stringency of hybridization and / or washing conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.
[0102] The "Tm value" herein refers to the temperature at which the double-stranded portion of a polynucleotide denatures into a single strand and the double strands and single strands exist in a 1:1 ratio.
[0103] As used herein, "mutant" refers to a natural mutant caused by polymorphism, mutation, or the like in the case of nucleic acids; a variant comprising a deletion, substitution, addition, or insertion of one, two, three, or more bases in any of the base sequences of SEQ ID NOs: 1 to 684, or a base sequence in which u is t in such base sequence, or a partial sequence thereof; a variant comprising a deletion, substitution, addition, or insertion of one, two, three, or more bases in any of the base sequences of SEQ ID NOs: 1 to 684, or a base sequence in which u is t in such base sequence, or a partial sequence thereof; a mutant exhibiting about 90% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more identity with such base sequence or a partial sequence thereof; or a nucleic acid that hybridizes to a polynucleotide or oligonucleotide comprising such base sequence or a partial sequence thereof under the stringent conditions defined above.
[0104] In this specification, "a plurality of" refers to an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.
[0105] In this specification, mutants can be prepared using known techniques such as site-directed mutagenesis and mutation introduction using PCR.
[0106] As used herein, "% identity" can be determined using the above-mentioned protein or gene search systems utilizing BLAST or FASTA, with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, pp. 203-214; Altschul, SF et al., 1990, Journal of Molecular Biology, Vol. 215, pp. 403-410; Pearson, WR et al., 1988, Proc. Natl. Acad. Sci. USA, Vol. 85, pp. 2444-2448).
[0107] In this specification, "derivative" refers to modified nucleic acids, and includes, but is not limited to, derivatives labeled with fluorophores, etc., derivatives containing modified nucleotides (for example, nucleotides containing groups such as halogens, alkyl groups such as methyl groups, alkoxy groups such as methoxy groups, thio groups, carboxymethyl groups, and nucleotides that have undergone base reconstruction, double bond saturation, deamination, replacement of oxygen molecules with sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, PE et al., 1991, Science, Vol. 254, p1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p5401-5404), etc.
[0108] In this specification, the "nucleic acid" that can specifically bind to the polynucleotide selected from the miRNA as a prostate cancer marker is a synthetic or modulated nucleic acid, specifically, a "nucleic acid probe" or a "primer", which is used directly or indirectly to detect the presence of prostate cancer in a subject, or to diagnose the presence of prostate cancer, the extent of the disease, the improvement of prostate cancer, the degree of improvement, the sensitivity to prostate cancer treatment, or to screen for candidate substances useful for the prevention, improvement or treatment of prostate cancer. They include nucleotides, oligonucleotides and polynucleotides that can specifically recognize and bind to the transcript shown in any one of sequence numbers 1 to 684 or its cDNA synthetic nucleic acid in vivo, especially in specimens such as body fluids such as blood and urine, in relation to the incidence of prostate cancer. Based on the above properties, these nucleotides, oligonucleotides and polynucleotides can be effectively used as probes for detecting the above genes expressed in vivo, in tissues, cells, etc., and can also be effectively used as primers for amplifying the above genes expressed in vivo.
[0109] The term "detection" used in this specification can be replaced with the term "inspection," "measurement," "detection," or "determination support." Furthermore, the term "evaluation" used in this specification includes supporting diagnosis or evaluation based on the results of an inspection or measurement.
[0110] As used herein, the term "subject" refers to mammals, including humans, primates such as chimpanzees, pets such as dogs and cats, livestock such as cattle, horses, sheep, and goats, and rodents such as mice and rats. Furthermore, the term "healthy subject" refers to a mammal that does not have the cancer being tested.
[0111] As used herein, "P" or "P-value" indicates the probability of observing a statistically significant difference compared to the statistic calculated from the data under the null hypothesis in a statistical test. Therefore, a smaller "P" or "P-value" indicates a significant difference between the comparison subjects.
[0112] In this specification, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, prostate cancer can be detected early, leading to complete resection of the cancer and a reduction in the recurrence rate.
[0113] In this specification, "specificity" refers to (the number of true negatives) / (the number of true negatives + the number of false positives). If the specificity is high, unnecessary additional examinations caused by misidentifying healthy individuals as prostate cancer patients can be prevented, thereby reducing the burden on patients and medical expenses.
[0114] In this specification, "accuracy" refers to the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the proportion of correct discrimination results for all samples and is the primary indicator for evaluating detection performance.
[0115] The "specimen" used in this specification as an object of determination, detection, or diagnosis refers to tissues and biological materials whose gene expression changes with the occurrence, progression, and treatment of prostate cancer. Specifically, it refers to prostate tissue and its surrounding blood vessels, lymph nodes, and organs. It also refers to suspected metastatic organs, skin, and body fluids such as blood, urine, saliva, sweat, and tissue leaching fluid, serum and plasma prepared from blood, as well as feces and hair. It further refers to biological samples extracted from these, specifically, genes such as RNA and miRNA.
[0116] As used herein, the term "hsa-miR-4443 gene" or "hsa-miR-4443" includes the hsa-miR-4443 gene described in SEQ ID NO: 1 (miRBase Accession No. MIMAT0018961) and homologs or orthologs in other species. The hsa-miR-4443 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4443", "hsa-mir-4443" (miRBase Accession No. MI0016786, SEQ ID NO: 188) is known to have a hairpin-like structure.
[0117] As used herein, the term “hsa-miR-1908-5p gene” or “hsa-miR-1908-5p” includes the hsa-miR-1908-5p gene described in SEQ ID NO: 2 (miRBase Accession No. MIMAT0007881) and homologs or orthologs in other biological species. The hsa-miR-1908-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, as a precursor of “hsa-miR-1908-5p”, “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 189) is known to have a hairpin-like structure.
[0118] As used herein, the term “hsa-miR-4257 gene” or “hsa-miR-4257” includes the hsa-miR-4257 gene described in SEQ ID NO: 3 (miRBase Accession No. MIMAT0016878) and homologs or orthologs in other species. The hsa-miR-4257 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4257”, “hsa-mir-4257” (miRBase Accession No. MI0015856, SEQ ID NO: 190) is known to have a hairpin-like structure.
[0119] As used herein, the term “hsa-miR-3197 gene” or “hsa-miR-3197” includes the hsa-miR-3197 gene described in SEQ ID NO: 4 (miRBase Accession No. MIMAT0015082) and homologs or orthologs in other species. The hsa-miR-3197 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3197,” “hsa-mir-3197” (miRBase Accession No. MI0014245, SEQ ID NO: 191) is known to have a hairpin-like structure.
[0120] As used herein, the term “hsa-miR-3188 gene” or “hsa-miR-3188” includes the hsa-miR-3188 gene described in SEQ ID NO: 5 (miRBase Accession No. MIMAT0015070) and homologs or orthologs in other species. The hsa-miR-3188 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3188,” “hsa-mir-3188” (miRBase Accession No. MI0014232, SEQ ID NO: 192) is known to have a hairpin-like structure.
[0121] As used herein, the term "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" includes the hsa-miR-4649-5p gene described in SEQ ID NO: 6 (miRBase Accession No. MIMAT0019711) and homologs or orthologs in other species. The hsa-miR-4649-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4649-5p", "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 193) is known to have a hairpin-like structure.
[0122] As used herein, the term "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" includes the hsa-miR-1343-3p gene described in SEQ ID NO: 7 (miRBase Accession No. MIMAT0019776) and homologs or orthologs in other species. The hsa-miR-1343-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-1343-3p", "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 194) is known to have a hairpin-like structure.
[0123] As used herein, the term "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" includes the hsa-miR-6861-5p gene described in SEQ ID NO: 8 (miRBase Accession No. MIMAT0027623) and homologs or orthologs in other species. The hsa-miR-6861-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6861-5p", "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 195) is known to have a hairpin-like structure.
[0124] As used herein, the term "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" includes the hsa-miR-1343-5p gene described in SEQ ID NO: 9 (miRBase Accession No. MIMAT0027038) and homologs or orthologs in other species. The hsa-miR-1343-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-1343-5p", "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 194) is known to have a hairpin-like structure.
[0125] As used herein, the term “hsa-miR-642b-3p gene” or “hsa-miR-642b-3p” includes the hsa-miR-642b-3p gene described in SEQ ID NO: 10 (miRBase Accession No. MIMAT0018444) and homologs or orthologs in other biological species. The hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of “hsa-miR-642b-3p,” “hsa-mir-642b” (miRBase Accession No. MI0016685, SEQ ID NO: 196) is known to have a hairpin-like structure.
[0126] As used herein, the term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" includes the hsa-miR-6741-5p gene described in SEQ ID NO: 11 (miRBase Accession No. MIMAT0027383) and homologs or orthologs in other species. The hsa-miR-6741-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6741-5p", "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 197) is known to have a hairpin-like structure.
[0127] As used herein, the term "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" includes the hsa-miR-4745-5p gene described in SEQ ID NO: 12 (miRBase Accession No. MIMAT0019878) and homologs or orthologs in other species. The hsa-miR-4745-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4745-5p", "hsa-mir-4745" (miRBase Accession No. MI0017384, SEQ ID NO: 198) is known to have a hairpin-like structure.
[0128] As used herein, the term “hsa-miR-6826-5p gene” or “hsa-miR-6826-5p” includes the hsa-miR-6826-5p gene described in SEQ ID NO: 13 (miRBase Accession No. MIMAT0027552) and homologs or orthologs in other species. The hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6826-5p,” “hsa-mir-6826” (miRBase Accession No. MI0022671, SEQ ID NO: 199) is known to have a hairpin-like structure.
[0129] As used herein, the term "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" includes the hsa-miR-3663-3p gene described in SEQ ID NO: 14 (miRBase Accession No. MIMAT0018085) and homologs or orthologs in other species. The hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3663-3p", "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 200) is known to have a hairpin-like structure.
[0130] As used herein, the term “hsa-miR-3131 gene” or “hsa-miR-3131” includes the hsa-miR-3131 gene described in SEQ ID NO: 15 (miRBase Accession No. MIMAT0014996) and homologs or orthologs in other species. The hsa-miR-3131 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3131,” “hsa-mir-3131” (miRBase Accession No. MI0014151, SEQ ID NO: 201) is known to have a hairpin-like structure.
[0131] As used herein, the term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" includes the hsa-miR-92a-2-5p gene described in SEQ ID NO: 16 (miRBase Accession No. MIMAT0004508) and homologs or orthologs in other biological species. The hsa-miR-92a-2-5p gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. Furthermore, as a precursor of "hsa-miR-92a-2-5p", "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 202) is known to have a hairpin-like structure.
[0132] As used herein, the term “hsa-miR-4258 gene” or “hsa-miR-4258” includes the hsa-miR-4258 gene described in SEQ ID NO: 17 (miRBase Accession No. MIMAT0016879) and homologs or orthologs in other species. The hsa-miR-4258 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4258”, “hsa-mir-4258” (miRBase Accession No. MI0015857, SEQ ID NO: 203) is known to have a hairpin-like structure.
[0133] As used herein, the term "hsa-miR-4448 gene" or "hsa-miR-4448" includes the hsa-miR-4448 gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0018967) and homologs or orthologs in other species. The hsa-miR-4448 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4448", "hsa-mir-4448" (miRBase Accession No. MI0016791, SEQ ID NO: 204) is known to have a hairpin-like structure.
[0134] As used herein, the term "hsa-miR-6125 gene" or "hsa-miR-6125" includes the hsa-miR-6125 gene described in SEQ ID NO: 19 (miRBase Accession No. MIMAT0024598) and homologs or orthologs in other species. The hsa-miR-6125 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of "hsa-miR-6125," "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 205) is known to have a hairpin-like structure.
[0135] As used herein, the term "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" includes the hsa-miR-6880-5p gene described in SEQ ID NO: 20 (miRBase Accession No. MIMAT0027660) and homologs or orthologs in other species. The hsa-miR-6880-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6880-5p", "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 206) is known to have a hairpin-like structure.
[0136] As used herein, the term "hsa-miR-6132 gene" or "hsa-miR-6132" includes the hsa-miR-6132 gene described in SEQ ID NO: 21 (miRBase Accession No. MIMAT0024616) and homologs or orthologs in other species. The hsa-miR-6132 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, 4, pp. 552-564. Furthermore, as a precursor of "hsa-miR-6132," "hsa-mir-6132" (miRBase Accession No. MI0021277, SEQ ID NO: 207) is known to have a hairpin-like structure.
[0137] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" includes the hsa-miR-4467 gene described in SEQ ID NO: 22 (miRBase Accession No. MIMAT0018994) and homologs or orthologs in other species. The hsa-miR-4467 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4467", "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 208) is known to have a hairpin-like structure.
[0138] As used herein, the term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" includes the hsa-miR-6749-5p gene described in SEQ ID NO: 23 (miRBase Accession No. MIMAT0027398) and homologs or orthologs in other species. The hsa-miR-6749-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6749-5p", "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 209) is known to have a hairpin-like structure.
[0139] As used herein, the term "hsa-miR-2392 gene" or "hsa-miR-2392" includes the hsa-miR-2392 gene described in SEQ ID NO: 24 (miRBase Accession No. MIMAT0019043) and homologs or orthologs in other species. The hsa-miR-2392 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-2392", "hsa-mir-2392" (miRBase Accession No. MI0016870, SEQ ID NO: 210) is known to have a hairpin-like structure.
[0140] As used herein, the term “hsa-miR-1273g-3p gene” or “hsa-miR-1273g-3p” includes the hsa-miR-1273g-3p gene described in SEQ ID NO: 25 (miRBase Accession No. MIMAT0022742) and homologs or orthologs in other biological species. The hsa-miR-1273g-3p gene can be obtained by the method described in Reshmi G et al., 2011, Genomics, Vol. 97, pp. 333-340. Furthermore, as a precursor of “hsa-miR-1273g-3p,” “hsa-mir-1273g” (miRBase Accession No. MI0018003, SEQ ID NO: 211) is known to have a hairpin-like structure.
[0141] As used herein, the term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" includes the hsa-miR-4746-3p gene described in SEQ ID NO: 26 (miRBase Accession No. MIMAT0019881) and homologs or orthologs in other species. The hsa-miR-4746-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4746-3p", "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 212) is known to have a hairpin-like structure.
[0142] As used herein, the term “hsa-miR-1914-3p gene” or “hsa-miR-1914-3p” includes the hsa-miR-1914-3p gene described in SEQ ID NO: 27 (miRBase Accession No. MIMAT0007890) and homologs or orthologs in other biological species. The hsa-miR-1914-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of “hsa-miR-1914-3p,” “hsa-mir-1914” (miRBase Accession No. MI0008335, SEQ ID NO: 213) is known to have a hairpin-like structure.
[0143] As used herein, the term "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" includes the hsa-miR-7845-5p gene described in SEQ ID NO: 28 (miRBase Accession No. MIMAT0030420) and homologs or orthologs in other species. The hsa-miR-7845-5p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of "hsa-miR-7845-5p," "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 214) is known to have a hairpin-like structure.
[0144] As used herein, the term “hsa-miR-6726-5p gene” or “hsa-miR-6726-5p” includes the hsa-miR-6726-5p gene described in SEQ ID NO: 29 (miRBase Accession No. MIMAT0027353) and homologs or orthologs in other species. The hsa-miR-6726-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6726-5p,” “hsa-mir-6726” (miRBase Accession No. MI0022571, SEQ ID NO: 215) is known to have a hairpin-like structure.
[0145] As used herein, the term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" includes the hsa-miR-128-2-5p gene described in SEQ ID NO: 30 (miRBase Accession No. MIMAT0031095) and homologs or orthologs in other species. The hsa-miR-128-2-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-128-2-5p", "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 216) is known to have a hairpin-like structure.
[0146] As used herein, the term “hsa-miR-4651 gene” or “hsa-miR-4651” includes the hsa-miR-4651 gene described in SEQ ID NO: 31 (miRBase Accession No. MIMAT0019715) and homologs or orthologs in other species. The hsa-miR-4651 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4651,” “hsa-mir-4651” (miRBase Accession No. MI0017279, SEQ ID NO: 217) is known to have a hairpin-like structure.
[0147] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" includes the hsa-miR-6765-3p gene described in SEQ ID NO: 32 (miRBase Accession No. MIMAT0027431) and homologs or orthologs in other species. The hsa-miR-6765-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6765-3p", "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 218) is known to have a hairpin-like structure.
[0148] As used herein, the term “hsa-miR-3185 gene” or “hsa-miR-3185” includes the hsa-miR-3185 gene described in SEQ ID NO: 33 (miRBase Accession No. MIMAT0015065) and homologs or orthologs in other species. The hsa-miR-3185 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3185,” “hsa-mir-3185” (miRBase Accession No. MI0014227, SEQ ID NO: 219) is known to have a hairpin-like structure.
[0149] As used herein, the term "hsa-miR-4792 gene" or "hsa-miR-4792" includes the hsa-miR-4792 gene described in SEQ ID NO: 34 (miRBase Accession No. MIMAT0019964) and homologs or orthologs in other species. The hsa-miR-4792 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4792," "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 220) is known to have a hairpin-like structure.
[0150] As used herein, the term “hsa-miR-6887-5p gene” or “hsa-miR-6887-5p” includes the hsa-miR-6887-5p gene described in SEQ ID NO: 35 (miRBase Accession No. MIMAT0027674) and homologs or orthologs in other species. The hsa-miR-6887-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6887-5p,” “hsa-mir-6887” (miRBase Accession No. MI0022734, SEQ ID NO: 221) is known to have a hairpin-like structure.
[0151] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" includes the hsa-miR-5572 gene described in SEQ ID NO: 36 (miRBase Accession No. MIMAT0022260) and homologs or orthologs in other species. The hsa-miR-5572 gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. Furthermore, as a precursor of "hsa-miR-5572," "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 222) is known to have a hairpin-like structure.
[0152] As used herein, the term “hsa-miR-3619-3p gene” or “hsa-miR-3619-3p” includes the hsa-miR-3619-3p gene described in SEQ ID NO: 37 (miRBase Accession No. MIMAT0019219) and homologs or orthologs in other biological species. The hsa-miR-3619-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of “hsa-miR-3619-3p,” “hsa-mir-3619” (miRBase Accession No. MI0016009, SEQ ID NO: 223) is known to have a hairpin-like structure.
[0153] As used herein, the term “hsa-miR-6780b-5p gene” or “hsa-miR-6780b-5p” includes the hsa-miR-6780b-5p gene described in SEQ ID NO: 38 (miRBase Accession No. MIMAT0027572) and homologs or orthologs in other species. The hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6780b-5p,” “hsa-mir-6780b” (miRBase Accession No. MI0022681, SEQ ID NO: 224) is known to have a hairpin-like structure.
[0154] As used herein, the term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" includes the hsa-miR-4707-5p gene described in SEQ ID NO: 39 (miRBase Accession No. MIMAT0019807) and homologs or orthologs in other species. The hsa-miR-4707-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4707-5p", "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 225) is known to have a hairpin-like structure.
[0155] As used herein, the term “hsa-miR-8063 gene” or “hsa-miR-8063” includes the hsa-miR-8063 gene described in SEQ ID NO: 40 (miRBase Accession No. MIMAT0030990) and homologs or orthologs in other species. The hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8063”, “hsa-mir-8063” (miRBase Accession No. MI0025899, SEQ ID NO: 226) is known to have a hairpin-like structure.
[0156] As used herein, the term "hsa-miR-4454 gene" or "hsa-miR-4454" includes the hsa-miR-4454 gene described in SEQ ID NO: 41 (miRBase Accession No. MIMAT0018976) and homologs or orthologs in other species. The hsa-miR-4454 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4454", "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 227) is known to have a hairpin-like structure.
[0157] As used herein, the term "hsa-miR-4525 gene" or "hsa-miR-4525" includes the hsa-miR-4525 gene described in SEQ ID NO: 42 (miRBase Accession No. MIMAT0019064) and homologs or orthologs in other species. The hsa-miR-4525 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4525," "hsa-mir-4525" (miRBase Accession No. MI0016892, SEQ ID NO: 228) is known to have a hairpin-like structure.
[0158] As used herein, the term “hsa-miR-7975 gene” or “hsa-miR-7975” includes the hsa-miR-7975 gene described in SEQ ID NO: 43 (miRBase Accession No. MIMAT0031178) and homologs or orthologs in other biological species. The hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, Online Edition. In addition, as a precursor of “hsa-miR-7975”, “hsa-mir-7975” (miRBase Accession No. MI0025751, SEQ ID NO: 229) is known to have a hairpin-like structure.
[0159] As used herein, the term "hsa-miR-744-5p gene" or "hsa-miR-744-5p" includes the hsa-miR-744-5p gene described in SEQ ID NO: 44 (miRBase Accession No. MIMAT0004945) and homologs or orthologs in other species. The hsa-miR-744-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-744-5p", "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 230) is known to have a hairpin-like structure.
[0160] As used herein, the term "hsa-miR-3135b gene" or "hsa-miR-3135b" includes the hsa-miR-3135b gene described in SEQ ID NO: 45 (miRBase Accession No. MIMAT0018985) and homologs or orthologs in other species. The hsa-miR-3135b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-3135b", "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 231) is known to have a hairpin-like structure.
[0161] As used herein, the term “hsa-miR-4648 gene” or “hsa-miR-4648” includes the hsa-miR-4648 gene described in SEQ ID NO: 46 (miRBase Accession No. MIMAT0019710) and homologs or orthologs in other species. The hsa-miR-4648 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4648,” “hsa-mir-4648” (miRBase Accession No. MI0017275, SEQ ID NO: 232) is known to have a hairpin-like structure.
[0162] As used herein, the term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" includes the hsa-miR-6816-5p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0027532) and homologs or orthologs in other species. The hsa-miR-6816-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6816-5p", "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 233) is known to have a hairpin-like structure.
[0163] As used herein, the term “hsa-miR-4741 gene” or “hsa-miR-4741” includes the hsa-miR-4741 gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0019871) and homologs or orthologs in other species. The hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4741,” “hsa-mir-4741” (miRBase Accession No. MI0017379, SEQ ID NO: 234) is known to have a hairpin-like structure.
[0164] As used herein, the term "hsa-miR-7150 gene" or "hsa-miR-7150" includes the hsa-miR-7150 gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0028211) and homologs or orthologs in other species. The hsa-miR-7150 gene can be obtained by the method described in Oulas A et al., 2009, Nucleic Acids Res, Vol. 37, pp. 3276-3287. In addition, as a precursor of "hsa-miR-7150", "hsa-mir-7150" (miRBase Accession No. MI0023610, SEQ ID NO: 235) is known to have a hairpin-like structure.
[0165] As used herein, the term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" includes the hsa-miR-6791-5p gene described in SEQ ID NO: 50 (miRBase Accession No. MIMAT0027482) and homologs or orthologs in other species. The hsa-miR-6791-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6791-5p", "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 236) is known to have a hairpin-like structure.
[0166] As used herein, the term “hsa-miR-1247-3p gene” or “hsa-miR-1247-3p” includes the hsa-miR-1247-3p gene described in SEQ ID NO: 51 (miRBase Accession No. MIMAT0022721) and homologs or orthologs in other biological species. The hsa-miR-1247-3p gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1247-3p”, “hsa-mir-1247” (miRBase Accession No. MI0006382, SEQ ID NO: 237) is known to have a hairpin-like structure.
[0167] As used herein, the term “hsa-miR-7977 gene” or “hsa-miR-7977” includes the hsa-miR-7977 gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0031180) and homologs or orthologs in other biological species. The hsa-miR-7977 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, Online Edition. In addition, as a precursor of “hsa-miR-7977”, “hsa-mir-7977” (miRBase Accession No. MI0025753, SEQ ID NO: 238) is known to form a hairpin-like structure.
[0168] As used herein, the term "hsa-miR-4497 gene" or "hsa-miR-4497" includes the hsa-miR-4497 gene described in SEQ ID NO: 53 (miRBase Accession No. MIMAT0019032) and homologs or orthologs in other species. The hsa-miR-4497 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4497", "hsa-mir-4497" (miRBase Accession No. MI0016859, SEQ ID NO: 239) is known to have a hairpin-like structure.
[0169] As used herein, the term "hsa-miR-6090 gene" or "hsa-miR-6090" includes the hsa-miR-6090 gene described in SEQ ID NO: 54 (miRBase Accession No. MIMAT0023715) and homologs or orthologs in other species. The hsa-miR-6090 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor of "hsa-miR-6090", "hsa-mir-6090" (miRBase Accession No. MI0020367, SEQ ID NO: 240) is known to have a hairpin-like structure.
[0170] As used herein, the term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" includes the hsa-miR-6781-5p gene described in SEQ ID NO: 55 (miRBase Accession No. MIMAT0027462) and homologs or orthologs in other species. The hsa-miR-6781-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6781-5p", "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 241) is known to have a hairpin-like structure.
[0171] As used herein, the term "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" includes the hsa-miR-6870-5p gene described in SEQ ID NO: 56 (miRBase Accession No. MIMAT0027640) and homologs or orthologs in other species. The hsa-miR-6870-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6870-5p", "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 242) is known to have a hairpin-like structure.
[0172] As used herein, the term “hsa-miR-6729-5p gene” or “hsa-miR-6729-5p” includes the hsa-miR-6729-5p gene described in SEQ ID NO: 57 (miRBase Accession No. MIMAT0027359) and homologs or orthologs in other species. The hsa-miR-6729-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6729-5p,” “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 243) is known to have a hairpin-like structure.
[0173] As used herein, the term "hsa-miR-4530 gene" or "hsa-miR-4530" includes the hsa-miR-4530 gene described in SEQ ID NO: 58 (miRBase Accession No. MIMAT0019069) and homologs or orthologs in other species. The hsa-miR-4530 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4530", "hsa-mir-4530" (miRBase Accession No. MI0016897, SEQ ID NO: 244) is known to have a hairpin-like structure.
[0174] As used herein, the term “hsa-miR-7847-3p gene” or “hsa-miR-7847-3p” includes the hsa-miR-7847-3p gene described in SEQ ID NO: 59 (miRBase Accession No. MIMAT0030422) and homologs or orthologs in other species. The hsa-miR-7847-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of “hsa-miR-7847-3p,” “hsa-mir-7847” (miRBase Accession No. MI0025517, SEQ ID NO: 245) is known to have a hairpin-like structure.
[0175] As used herein, the term "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" includes the hsa-miR-6825-5p gene described in SEQ ID NO: 60 (miRBase Accession No. MIMAT0027550) and homologs or orthologs in other species. The hsa-miR-6825-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6825-5p", "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 246) is known to have a hairpin-like structure.
[0176] As used herein, the term “hsa-miR-4674 gene” or “hsa-miR-4674” includes the hsa-miR-4674 gene described in SEQ ID NO: 61 (miRBase Accession No. MIMAT0019756) and homologs or orthologs in other species. The hsa-miR-4674 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, as a precursor of “hsa-miR-4674,” “hsa-mir-4674” (miRBase Accession No. MI0017305, SEQ ID NO: 247) is known to have a hairpin-like structure.
[0177] As used herein, the term “hsa-miR-3917 gene” or “hsa-miR-3917” includes the hsa-miR-3917 gene described in SEQ ID NO: 62 (miRBase Accession No. MIMAT0018191) and homologs or orthologs in other species. The hsa-miR-3917 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of “hsa-miR-3917,” “hsa-mir-3917” (miRBase Accession No. MI0016423, SEQ ID NO: 248) is known to have a hairpin-like structure.
[0178] As used herein, the term "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" includes the hsa-miR-4707-3p gene described in SEQ ID NO: 63 (miRBase Accession No. MIMAT0019808) and homologs or orthologs in other species. The hsa-miR-4707-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4707-3p", "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 225) is known to have a hairpin-like structure.
[0179] As used herein, the term “hsa-miR-6885-5p gene” or “hsa-miR-6885-5p” includes the hsa-miR-6885-5p gene described in SEQ ID NO: 64 (miRBase Accession No. MIMAT0027670) and homologs or orthologs in other species. The hsa-miR-6885-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6885-5p,” “hsa-mir-6885” (miRBase Accession No. MI0022732, SEQ ID NO: 249) is known to have a hairpin-like structure.
[0180] As used herein, the term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" includes the hsa-miR-6722-3p gene described in SEQ ID NO: 65 (miRBase Accession No. MIMAT0025854) and homologs or orthologs in other species. The hsa-miR-6722-3p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6722-3p", "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 250) is known to have a hairpin-like structure.
[0181] As used herein, the term "hsa-miR-4516 gene" or "hsa-miR-4516" includes the hsa-miR-4516 gene described in SEQ ID NO: 66 (miRBase Accession No. MIMAT0019053) and homologs or orthologs in other species. The hsa-miR-4516 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4516," "hsa-mir-4516" (miRBase Accession No. MI0016882, SEQ ID NO: 251) is known to have a hairpin-like structure.
[0182] As used herein, the term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" includes the hsa-miR-6757-5p gene described in SEQ ID NO: 67 (miRBase Accession No. MIMAT0027414) and homologs or orthologs in other species. The hsa-miR-6757-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6757-5p", "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 252) is known to have a hairpin-like structure.
[0183] As used herein, the term "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" includes the hsa-miR-6840-3p gene described in SEQ ID NO: 68 (miRBase Accession No. MIMAT0027583) and homologs or orthologs in other species. The hsa-miR-6840-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6840-3p", "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 253) is known to have a hairpin-like structure.
[0184] As used herein, the term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" includes the hsa-miR-5195-3p gene described in SEQ ID NO: 69 (miRBase Accession No. MIMAT0021127) and homologs or orthologs in other species. The hsa-miR-5195-3p gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, Vol. 25, pp. 1389-1399. Furthermore, as a precursor of "hsa-miR-5195-3p," "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 254) is known to have a hairpin-like structure.
[0185] As used herein, the term "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" includes the hsa-miR-6756-5p gene described in SEQ ID NO: 70 (miRBase Accession No. MIMAT0027412) and homologs or orthologs in other species. The hsa-miR-6756-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6756-5p", "hsa-mir-6756" (miRBase Accession No. MI0022601, SEQ ID NO: 255) is known to have a hairpin-like structure.
[0186] As used herein, the term "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" includes the hsa-miR-6800-5p gene described in SEQ ID NO: 71 (miRBase Accession No. MIMAT0027500) and homologs or orthologs in other species. The hsa-miR-6800-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6800-5p", "hsa-mir-6800" (miRBase Accession No. MI0022645, SEQ ID NO: 256) is known to have a hairpin-like structure.
[0187] As used herein, the term “hsa-miR-6727-5p gene” or “hsa-miR-6727-5p” includes the hsa-miR-6727-5p gene described in SEQ ID NO: 72 (miRBase Accession No. MIMAT0027355) and homologs or orthologs in other species. The hsa-miR-6727-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6727-5p,” “hsa-mir-6727” (miRBase Accession No. MI0022572, SEQ ID NO: 257) is known to have a hairpin-like structure.
[0188] As used herein, the term “hsa-miR-6126 gene” or “hsa-miR-6126” includes the hsa-miR-6126 gene described in SEQ ID NO: 73 (miRBase Accession No. MIMAT0024599) and homologs or orthologs in other species. The hsa-miR-6126 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of “hsa-miR-6126,” “hsa-mir-6126” (miRBase Accession No. MI0021260, SEQ ID NO: 258) is known to have a hairpin-like structure.
[0189] As used herein, the term “hsa-miR-6872-3p gene” or “hsa-miR-6872-3p” includes the hsa-miR-6872-3p gene described in SEQ ID NO: 74 (miRBase Accession No. MIMAT0027645) and homologs or orthologs in other species. The hsa-miR-6872-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6872-3p,” “hsa-mir-6872” (miRBase Accession No. MI0022719, SEQ ID NO: 259) is known to have a hairpin-like structure.
[0190] As used herein, the term "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" includes the hsa-miR-4446-3p gene described in SEQ ID NO: 75 (miRBase Accession No. MIMAT0018965) and homologs or orthologs in other species. The hsa-miR-4446-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4446-3p", "hsa-mir-4446" (miRBase Accession No. MI0016789, SEQ ID NO: 260) is known to have a hairpin-like structure.
[0191] As used herein, the term “hsa-miR-1268a gene” or “hsa-miR-1268a” includes the hsa-miR-1268a gene described in SEQ ID NO: 76 (miRBase Accession No. MIMAT0005922) and homologs or orthologs in other biological species. The hsa-miR-1268a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1268a”, “hsa-mir-1268a” (miRBase Accession No. MI0006405, SEQ ID NO: 261) is known to have a hairpin-like structure.
[0192] As used herein, the term “hsa-miR-1908-3p gene” or “hsa-miR-1908-3p” includes the hsa-miR-1908-3p gene described in SEQ ID NO: 77 (miRBase Accession No. MIMAT0026916) and homologs or orthologs in other biological species. The hsa-miR-1908-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, as a precursor of “hsa-miR-1908-3p”, “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 189) is known to have a hairpin-like structure.
[0193] As used herein, the term “hsa-miR-3679-5p gene” or “hsa-miR-3679-5p” includes the hsa-miR-3679-5p gene described in SEQ ID NO: 78 (miRBase Accession No. MIMAT0018104) and homologs or orthologs in other species. The hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of “hsa-miR-3679-5p,” “hsa-mir-3679” (miRBase Accession No. MI0016080, SEQ ID NO: 262) is known to have a hairpin-like structure.
[0194] As used herein, the term "hsa-miR-4534 gene" or "hsa-miR-4534" includes the hsa-miR-4534 gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0019073) and homologs or orthologs in other species. The hsa-miR-4534 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4534," "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 263) is known to have a hairpin-like structure.
[0195] As used herein, the term "hsa-miR-4675 gene" or "hsa-miR-4675" includes the hsa-miR-4675 gene described in SEQ ID NO: 80 (miRBase Accession No. MIMAT0019757) and homologs or orthologs in other species. The hsa-miR-4675 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4675", "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 264) is known to have a hairpin-like structure.
[0196] As used herein, the term “hsa-miR-7108-5p gene” or “hsa-miR-7108-5p” includes the hsa-miR-7108-5p gene described in SEQ ID NO: 81 (miRBase Accession No. MIMAT0028113) and homologs or orthologs in other species. The hsa-miR-7108-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-7108-5p,” “hsa-mir-7108” (miRBase Accession No. MI0022959, SEQ ID NO: 265) is known to have a hairpin-like structure.
[0197] As used herein, the term “hsa-miR-6799-5p gene” or “hsa-miR-6799-5p” includes the hsa-miR-6799-5p gene described in SEQ ID NO: 82 (miRBase Accession No. MIMAT0027498) and homologs or orthologs in other species. The hsa-miR-6799-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6799-5p,” “hsa-mir-6799” (miRBase Accession No. MI0022644, SEQ ID NO: 266) is known to have a hairpin-like structure.
[0198] As used herein, the term "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" includes the hsa-miR-4695-5p gene described in SEQ ID NO: 83 (miRBase Accession No. MIMAT0019788) and homologs or orthologs in other biological species. The hsa-miR-4695-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4695-5p", "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 267) is known to have a hairpin-like structure.
[0199] As used herein, the term “hsa-miR-3178 gene” or “hsa-miR-3178” includes the hsa-miR-3178 gene described in SEQ ID NO: 84 (miRBase Accession No. MIMAT0015055) and homologs or orthologs in other species. The hsa-miR-3178 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3178,” “hsa-mir-3178” (miRBase Accession No. MI0014212, SEQ ID NO: 268) is known to have a hairpin-like structure.
[0200] As used herein, the term "hsa-miR-5090 gene" or "hsa-miR-5090" includes the hsa-miR-5090 gene described in SEQ ID NO: 85 (miRBase Accession No. MIMAT0021082) and homologs or orthologs in other species. The hsa-miR-5090 gene can be obtained by the method described in Ding N et al., 2011, J Radiat Res, Vol. 52, pp. 425-432. Furthermore, as a precursor of "hsa-miR-5090", "hsa-mir-5090" (miRBase Accession No. MI0017979, SEQ ID NO: 269) is known to have a hairpin-like structure.
[0201] As used herein, the term “hsa-miR-3180 gene” or “hsa-miR-3180” includes the hsa-miR-3180 gene described in SEQ ID NO: 86 (miRBase Accession No. MIMAT0018178) and homologs or orthologs in other biological species. The hsa-miR-3180 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, as precursors of “hsa-miR-3180”, “hsa-mir-3180-4 and hsa-mir-3180-5” (miRBase Accession Nos. MI0016408 and MI0016409, SEQ ID NOs: 270 and 271) are known.
[0202] As used herein, the term "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" includes the hsa-miR-1237-5p gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0022946) and homologs or orthologs in other species. The hsa-miR-1237-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1237-5p", "hsa-mir-1237" (miRBase Accession No. MI0006327, SEQ ID NO: 272) is known to have a hairpin-like structure.
[0203] As used herein, the term "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" includes the hsa-miR-4758-5p gene described in SEQ ID NO: 88 (miRBase Accession No. MIMAT0019903) and homologs or orthologs in other species. The hsa-miR-4758-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4758-5p", "hsa-mir-4758" (miRBase Accession No. MI0017399, SEQ ID NO: 273) is known to have a hairpin-like structure.
[0204] As used herein, the term “hsa-miR-3184-5p gene” or “hsa-miR-3184-5p” includes the hsa-miR-3184-5p gene described in SEQ ID NO: 89 (miRBase Accession No. MIMAT0015064) and homologs or orthologs in other species. The hsa-miR-3184-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3184-5p,” “hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 274) is known to have a hairpin-like structure.
[0205] As used herein, the term “hsa-miR-4286 gene” or “hsa-miR-4286” includes the hsa-miR-4286 gene described in SEQ ID NO: 90 (miRBase Accession No. MIMAT0016916) and homologs or orthologs in other species. The hsa-miR-4286 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4286”, “hsa-mir-4286” (miRBase Accession No. MI0015894, SEQ ID NO: 275) is known to have a hairpin-like structure.
[0206] As used herein, the term “hsa-miR-6784-5p gene” or “hsa-miR-6784-5p” includes the hsa-miR-6784-5p gene described in SEQ ID NO: 91 (miRBase Accession No. MIMAT0027468) and homologs or orthologs in other species. The hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6784-5p,” “hsa-mir-6784” (miRBase Accession No. MI0022629, SEQ ID NO: 276) is known to have a hairpin-like structure.
[0207] As used herein, the term “hsa-miR-6768-5p gene” or “hsa-miR-6768-5p” includes the hsa-miR-6768-5p gene described in SEQ ID NO: 92 (miRBase Accession No. MIMAT0027436) and homologs or orthologs in other species. The hsa-miR-6768-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6768-5p,” “hsa-mir-6768” (miRBase Accession No. MI0022613, SEQ ID NO: 277) is known to have a hairpin-like structure.
[0208] As used herein, the term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" includes the hsa-miR-6785-5p gene described in SEQ ID NO: 93 (miRBase Accession No. MIMAT0027470) and homologs or orthologs in other species. The hsa-miR-6785-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6785-5p", "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 278) is known to have a hairpin-like structure.
[0209] As used herein, the term "hsa-miR-4706 gene" or "hsa-miR-4706" includes the hsa-miR-4706 gene described in SEQ ID NO: 94 (miRBase Accession No. MIMAT0019806) and homologs or orthologs in other species. The hsa-miR-4706 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4706", "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 279) is known to have a hairpin-like structure.
[0210] As used herein, the term “hsa-miR-711 gene” or “hsa-miR-711” includes the hsa-miR-711 gene described in SEQ ID NO: 95 (miRBase Accession No. MIMAT0012734) and homologs or orthologs in other species. The hsa-miR-711 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, Vol. 9, p39. In addition, as a precursor of “hsa-miR-711”, “hsa-mir-711” (miRBase Accession No. MI0012488, SEQ ID NO: 280) is known to have a hairpin-like structure.
[0211] As used herein, the term “hsa-miR-1260a gene” or “hsa-miR-1260a” includes the hsa-miR-1260a gene described in SEQ ID NO: 96 (miRBase Accession No. MIMAT0005911) and homologs or orthologs in other biological species. The hsa-miR-1260a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1260a”, “hsa-mir-1260a” (miRBase Accession No. MI0006394, SEQ ID NO: 281) is known to have a hairpin-like structure.
[0212] As used herein, the term "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" includes the hsa-miR-6746-5p gene described in SEQ ID NO: 97 (miRBase Accession No. MIMAT0027392) and homologs or orthologs in other species. The hsa-miR-6746-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6746-5p", "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 282) is known to have a hairpin-like structure.
[0213] As used herein, the term “hsa-miR-6089 gene” or “hsa-miR-6089” includes the hsa-miR-6089 gene described in SEQ ID NO: 98 (miRBase Accession No. MIMAT0023714) and homologs or orthologs in other biological species. The hsa-miR-6089 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, as precursors of “hsa-miR-6089”, “hsa-mir-6089-1 and hsa-mir-6089-2” (miRBase Accession Nos. MI0020366 and MI0023563, SEQ ID NOs. 283 and 284) are known.
[0214] As used herein, the term "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" includes the hsa-miR-6821-5p gene described in SEQ ID NO: 99 (miRBase Accession No. MIMAT0027542) and homologs or orthologs in other species. The hsa-miR-6821-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6821-5p", "hsa-mir-6821" (miRBase Accession No. MI0022666, SEQ ID NO: 285) is known to have a hairpin-like structure.
[0215] As used herein, the term "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" includes the hsa-miR-4667-5p gene described in SEQ ID NO: 100 (miRBase Accession No. MIMAT0019743) and homologs or orthologs in other species. The hsa-miR-4667-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4667-5p", "hsa-mir-4667" (miRBase Accession No. MI0017297, SEQ ID NO: 286) is known to have a hairpin-like structure.
[0216] As used herein, the term “hsa-miR-8069 gene” or “hsa-miR-8069” includes the hsa-miR-8069 gene described in SEQ ID NO: 101 (miRBase Accession No. MIMAT0030996) and homologs or orthologs in other species. The hsa-miR-8069 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8069,” “hsa-mir-8069” (miRBase Accession No. MI0025905, SEQ ID NO: 287) is known to have a hairpin-like structure.
[0217] As used herein, the term "hsa-miR-4726-5p gene" or "hsa-miR-4726-5p" includes the hsa-miR-4726-5p gene described in SEQ ID NO: 102 (miRBase Accession No. MIMAT0019845) and homologs or orthologs in other species. The hsa-miR-4726-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4726-5p", "hsa-mir-4726" (miRBase Accession No. MI0017363, SEQ ID NO: 288) is known to have a hairpin-like structure.
[0218] As used herein, the term “hsa-miR-6124 gene” or “hsa-miR-6124” includes the hsa-miR-6124 gene described in SEQ ID NO: 103 (miRBase Accession No. MIMAT0024597) and homologs or orthologs in other species. The hsa-miR-6124 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of “hsa-miR-6124,” “hsa-mir-6124” (miRBase Accession No. MI0021258, SEQ ID NO: 289) is known to have a hairpin-like structure.
[0219] As used herein, the term "hsa-miR-4532 gene" or "hsa-miR-4532" includes the hsa-miR-4532 gene described in SEQ ID NO: 104 (miRBase Accession No. MIMAT0019071) and homologs or orthologs in other species. The hsa-miR-4532 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4532," "hsa-mir-4532" (miRBase Accession No. MI0016899, SEQ ID NO: 290) is known to have a hairpin-like structure.
[0220] As used herein, the term "hsa-miR-4486 gene" or "hsa-miR-4486" includes the hsa-miR-4486 gene described in SEQ ID NO: 105 (miRBase Accession No. MIMAT0019020) and homologs or orthologs in other species. The hsa-miR-4486 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4486", "hsa-mir-4486" (miRBase Accession No. MI0016847, SEQ ID NO: 291) is known to have a hairpin-like structure.
[0221] As used herein, the term "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" includes the hsa-miR-4728-5p gene described in SEQ ID NO: 106 (miRBase Accession No. MIMAT0019849) and homologs or orthologs in other species. The hsa-miR-4728-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4728-5p", "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 292) is known to have a hairpin-like structure.
[0222] As used herein, the term "hsa-miR-4508 gene" or "hsa-miR-4508" includes the hsa-miR-4508 gene described in SEQ ID NO: 107 (miRBase Accession No. MIMAT0019045) and homologs or orthologs in other species. The hsa-miR-4508 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4508," "hsa-mir-4508" (miRBase Accession No. MI0016872, SEQ ID NO: 293) is known to have a hairpin-like structure.
[0223] As used herein, the term "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" includes the hsa-miR-128-1-5p gene described in SEQ ID NO: 108 (miRBase Accession No. MIMAT0026477) and homologs or orthologs in other species. The hsa-miR-128-1-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-128-1-5p," "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 294) is known to have a hairpin-like structure.
[0224] As used herein, the term "hsa-miR-4513 gene" or "hsa-miR-4513" includes the hsa-miR-4513 gene described in SEQ ID NO: 109 (miRBase Accession No. MIMAT0019050) and homologs or orthologs in other species. The hsa-miR-4513 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4513," "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 295) is known to have a hairpin-like structure.
[0225] As used herein, the term "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" includes the hsa-miR-6795-5p gene described in SEQ ID NO: 110 (miRBase Accession No. MIMAT0027490) and homologs or orthologs in other species. The hsa-miR-6795-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6795-5p", "hsa-mir-6795" (miRBase Accession No. MI0022640, SEQ ID NO: 296) is known to have a hairpin-like structure.
[0226] As used herein, the term “hsa-miR-4689 gene” or “hsa-miR-4689” includes the hsa-miR-4689 gene described in SEQ ID NO: 111 (miRBase Accession No. MIMAT0019778) and homologs or orthologs in other species. The hsa-miR-4689 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4689,” “hsa-mir-4689” (miRBase Accession No. MI0017322, SEQ ID NO: 297) is known to have a hairpin-like structure.
[0227] As used herein, the term "hsa-miR-6763-5p gene" or "hsa-miR-6763-5p" includes the hsa-miR-6763-5p gene described in SEQ ID NO: 112 (miRBase Accession No. MIMAT0027426) and homologs or orthologs in other species. The hsa-miR-6763-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6763-5p", "hsa-mir-6763" (miRBase Accession No. MI0022608, SEQ ID NO: 298) is known to have a hairpin-like structure.
[0228] As used herein, the term “hsa-miR-8072 gene” or “hsa-miR-8072” includes the hsa-miR-8072 gene described in SEQ ID NO: 113 (miRBase Accession No. MIMAT0030999) and homologs or orthologs in other species. The hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8072”, “hsa-mir-8072” (miRBase Accession No. MI0025908, SEQ ID NO: 299) is known to have a hairpin-like structure.
[0229] As used herein, the term "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" includes the hsa-miR-6765-5p gene described in SEQ ID NO: 114 (miRBase Accession No. MIMAT0027430) and homologs or orthologs in other species. The hsa-miR-6765-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6765-5p," "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 218) is known to have a hairpin-like structure.
[0230] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" includes the hsa-miR-4419b gene described in SEQ ID NO: 115 (miRBase Accession No. MIMAT0019034) and homologs or orthologs in other species. The hsa-miR-4419b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4419b," "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 300) is known to have a hairpin-like structure.
[0231] As used herein, the term “hsa-miR-7641 gene” or “hsa-miR-7641” includes the hsa-miR-7641 gene described in SEQ ID NO: 116 (miRBase Accession No. MIMAT0029782) and homologs or orthologs in other biological species. The hsa-miR-7641 gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, Vol. 36, pp. 353-358. In addition, as precursors of “hsa-miR-7641”, “hsa-mir-7641-1, hsa-mir-7641-2” (miRBase Accession Nos. MI0024975, MI0024976, SEQ ID NOs: 301, 302) are known as hairpin-like structure forming precursors of “hsa-miR-7641”.
[0232] As used herein, the term "hsa-miR-3928-3p gene" or "hsa-miR-3928-3p" includes the hsa-miR-3928-3p gene described in SEQ ID NO: 117 (miRBase Accession No. MIMAT0018205) and homologs or orthologs in other species. The hsa-miR-3928-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of "hsa-miR-3928-3p", "hsa-mir-3928" (miRBase Accession No. MI0016438, SEQ ID NO: 303) is known to have a hairpin-like structure.
[0233] As used herein, the term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" includes the hsa-miR-1227-5p gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0022941) and homologs or orthologs in other species. The hsa-miR-1227-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1227-5p", "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 304) is known to have a hairpin-like structure.
[0234] As used herein, the term "hsa-miR-4492 gene" or "hsa-miR-4492" includes the hsa-miR-4492 gene described in SEQ ID NO: 119 (miRBase Accession No. MIMAT0019027) and homologs or orthologs in other species. The hsa-miR-4492 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4492", "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 305) is known to have a hairpin-like structure.
[0235] As used herein, the term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" includes the hsa-miR-296-3p gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0004679) and homologs or orthologs in other species. The hsa-miR-296-3p gene can be obtained by the method described in houbaviy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Furthermore, as a precursor of "hsa-miR-296-3p", "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 306) is known to have a hairpin-like structure.
[0236] As used herein, the term "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" includes the hsa-miR-6769a-5p gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0027438) and homologs or orthologs in other species. The hsa-miR-6769a-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6769a-5p," "hsa-mir-6769a" (miRBase Accession No. MI0022614, SEQ ID NO: 307) is known to have a hairpin-like structure.
[0237] As used herein, the term "hsa-miR-6889-5p gene" or "hsa-miR-6889-5p" includes the hsa-miR-6889-5p gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0027678) and homologs or orthologs in other species. The hsa-miR-6889-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6889-5p," "hsa-mir-6889" (miRBase Accession No. MI0022736, SEQ ID NO: 308) is known to have a hairpin-like structure.
[0238] As used herein, the term "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" includes the hsa-miR-4632-5p gene described in SEQ ID NO: 123 (miRBase Accession No. MIMAT0022977) and homologs or orthologs in other species. The hsa-miR-4632-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4632-5p", "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 309) is known to have a hairpin-like structure.
[0239] As used herein, the term "hsa-miR-4505 gene" or "hsa-miR-4505" includes the hsa-miR-4505 gene described in SEQ ID NO: 124 (miRBase Accession No. MIMAT0019041) and homologs or orthologs in other species. The hsa-miR-4505 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4505," "hsa-mir-4505" (miRBase Accession No. MI0016868, SEQ ID NO: 310) is known to have a hairpin-like structure.
[0240] As used herein, the term "hsa-miR-3154 gene" or "hsa-miR-3154" includes the hsa-miR-3154 gene described in SEQ ID NO: 125 (miRBase Accession No. MIMAT0015028) and homologs or orthologs in other species. The hsa-miR-3154 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, as a precursor of "hsa-miR-3154", "hsa-mir-3154" (miRBase Accession No. MI0014182, SEQ ID NO: 311) is known to have a hairpin-like structure.
[0241] As used herein, the term "hsa-miR-3648 gene" or "hsa-miR-3648" includes the hsa-miR-3648 gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0018068) and homologs or orthologs in other species. The hsa-miR-3648 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Furthermore, as a precursor of "hsa-miR-3648", "hsa-mir-3648" (miRBase Accession No. MI0016048, SEQ ID NO: 312) is known to have a hairpin-like structure.
[0242] As used herein, the term "hsa-miR-4442 gene" or "hsa-miR-4442" includes the hsa-miR-4442 gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0018960) and homologs or orthologs in other species. The hsa-miR-4442 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4442", "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 313) is known to have a hairpin-like structure.
[0243] As used herein, the term “hsa-miR-3141 gene” or “hsa-miR-3141” includes the hsa-miR-3141 gene described in SEQ ID NO: 128 (miRBase Accession No. MIMAT0015010) and homologs or orthologs in other species. The hsa-miR-3141 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3141,” “hsa-mir-3141” (miRBase Accession No. MI0014165, SEQ ID NO: 314) is known to have a hairpin-like structure.
[0244] As used herein, the term "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" includes the hsa-miR-7113-3p gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0028124) and homologs or orthologs in other species. The hsa-miR-7113-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7113-3p", "hsa-mir-7113" (miRBase Accession No. MI0022964, SEQ ID NO: 315) is known to have a hairpin-like structure.
[0245] As used herein, the term "hsa-miR-6819-5p gene" or "hsa-miR-6819-5p" includes the hsa-miR-6819-5p gene described in SEQ ID NO: 130 (miRBase Accession No. MIMAT0027538) and homologs or orthologs in other species. The hsa-miR-6819-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6819-5p," "hsa-mir-6819" (miRBase Accession No. MI0022664, SEQ ID NO: 316) is known to have a hairpin-like structure.
[0246] As used herein, the term “hsa-miR-3195 gene” or “hsa-miR-3195” includes the hsa-miR-3195 gene described in SEQ ID NO: 131 (miRBase Accession No. MIMAT0015079) and homologs or orthologs in other species. The hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, as a precursor of “hsa-miR-3195”, “hsa-mir-3195” (miRBase Accession No. MI0014240, SEQ ID NO: 317) is known to have a hairpin-like structure.
[0247] As used herein, the term “hsa-miR-1199-5p gene” or “hsa-miR-1199-5p” includes the hsa-miR-1199-5p gene described in SEQ ID NO: 132 (miRBase Accession No. MIMAT0031119) and homologs or orthologs in other species. The hsa-miR-1199-5p gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, Vol. 42, pp. 391-402. Furthermore, as a precursor of “hsa-miR-1199-5p,” “hsa-mir-1199” (miRBase Accession No. MI0020340, SEQ ID NO: 318) is known to have a hairpin-like structure.
[0248] As used herein, the term "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" includes the hsa-miR-6738-5p gene described in SEQ ID NO: 133 (miRBase Accession No. MIMAT0027377) and homologs or orthologs in other species. The hsa-miR-6738-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6738-5p", "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 319) is known to have a hairpin-like structure.
[0249] As used herein, the term "hsa-miR-4656 gene" or "hsa-miR-4656" includes the hsa-miR-4656 gene described in SEQ ID NO: 134 (miRBase Accession No. MIMAT0019723) and homologs or orthologs in other species. The hsa-miR-4656 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4656," "hsa-mir-4656" (miRBase Accession No. MI0017284, SEQ ID NO: 320) is known to have a hairpin-like structure.
[0250] As used herein, the term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" includes the hsa-miR-6820-5p gene described in SEQ ID NO: 135 (miRBase Accession No. MIMAT0027540) and homologs or orthologs in other species. The hsa-miR-6820-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6820-5p," "hsa-mir-6820" (miRBase Accession No. MI0022665, SEQ ID NO: 321) is known to have a hairpin-like structure.
[0251] As used herein, the term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" includes the hsa-miR-615-5p gene described in SEQ ID NO: 136 (miRBase Accession No. MIMAT0004804) and homologs or orthologs in other species. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-615-5p", "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 322) is known to have a hairpin-like structure.
[0252] As used herein, the term “hsa-miR-486-3p gene” or “hsa-miR-486-3p” includes the hsa-miR-486-3p gene described in SEQ ID NO: 137 (miRBase Accession No. MIMAT0004762) and homologs or orthologs in other species. The hsa-miR-486-3p gene can be obtained by the method described in Fu H et al., 2005, FEBS Lett, Vol. 579, pp. 3849-3854. Furthermore, as precursors of “hsa-miR-486-3p,” “hsa-mir-486, hsa-mir-486-2” (miRBase Accession Nos. MI0002470, MI0023622, SEQ ID NOs. 323, 324) are known.
[0253] As used herein, the term "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" includes the hsa-miR-1225-3p gene described in SEQ ID NO: 138 (miRBase Accession No. MIMAT0005573) and homologs or orthologs in other species. The hsa-miR-1225-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1225-3p", "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 325) is known to have a hairpin-like structure.
[0254] As used herein, the term "hsa-miR-760 gene" or "hsa-miR-760" includes the hsa-miR-760 gene described in SEQ ID NO: 139 (miRBase Accession No. MIMAT0004957) and homologs or orthologs in other species. The hsa-miR-760 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, as a precursor of "hsa-miR-760", "hsa-mir-760" (miRBase Accession No. MI0005567, SEQ ID NO: 326) is known to have a hairpin-like structure.
[0255] As used herein, the term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" includes the hsa-miR-187-5p gene described in SEQ ID NO: 140 (miRBase Accession No. MIMAT0004561) and homologs or orthologs in other species. The hsa-miR-187-5p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. Furthermore, as a precursor of "hsa-miR-187-5p", "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 327) is known to have a hairpin-like structure.
[0256] As used herein, the term "hsa-miR-1203 gene" or "hsa-miR-1203" includes the hsa-miR-1203 gene described in SEQ ID NO: 141 (miRBase Accession No. MIMAT0005866) and homologs or orthologs in other species. The hsa-miR-1203 gene can be obtained by the method described in Marton S et al., 2008, Leukemia, Vol. 22, pp. 330-338. Furthermore, as a precursor of "hsa-miR-1203," "hsa-mir-1203" (miRBase Accession No. MI0006335, SEQ ID NO: 328) is known to have a hairpin-like structure.
[0257] As used herein, the term "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" includes the hsa-miR-7110-5p gene described in SEQ ID NO: 142 (miRBase Accession No. MIMAT0028117) and homologs or orthologs in other species. The hsa-miR-7110-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7110-5p", "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 329) is known to have a hairpin-like structure.
[0258] As used herein, the term "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" includes the hsa-miR-371a-5p gene described in SEQ ID NO: 143 (miRBase Accession No. MIMAT0004687) and homologs or orthologs in other biological species. The hsa-miR-371a-5p gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, Vol. 270, pp. 488-498. Furthermore, as a precursor of "hsa-miR-371a-5p", "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 330) is known to have a hairpin-like structure.
[0259] As used herein, the term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" includes the hsa-miR-939-5p gene described in SEQ ID NO: 144 (miRBase Accession No. MIMAT0004982) and homologs or orthologs in other species. The hsa-miR-939-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Furthermore, as a precursor of "hsa-miR-939-5p," "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 331) is known to have a hairpin-like structure.
[0260] As used herein, the term "hsa-miR-575 gene" or "hsa-miR-575" includes the hsa-miR-575 gene described in SEQ ID NO: 145 (miRBase Accession No. MIMAT0003240) and homologs or orthologs in other species. The hsa-miR-575 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-575," "hsa-mir-575" (miRBase Accession No. MI0003582, SEQ ID NO: 332) is known to have a hairpin-like structure.
[0261] As used herein, the term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" includes the hsa-miR-92b-5p gene described in SEQ ID NO: 146 (miRBase Accession No. MIMAT0004792) and homologs or orthologs in other species. The hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-92b-5p", "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 333) is known to have a hairpin-like structure.
[0262] As used herein, the term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" includes the hsa-miR-887-3p gene described in SEQ ID NO: 147 (miRBase Accession No. MIMAT0004951) and homologs or orthologs in other species. The hsa-miR-887-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, as a precursor of "hsa-miR-887-3p", "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 334) is known to have a hairpin-like structure.
[0263] As used herein, the term "hsa-miR-920 gene" or "hsa-miR-920" includes the hsa-miR-920 gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0004970) and homologs or orthologs in other species. The hsa-miR-920 gene can be obtained by the method described in Novotny GW et al., 2007, Int J Androl, Vol. 30, pp. 316-326. Furthermore, as a precursor of "hsa-miR-920," "hsa-mir-920" (miRBase Accession No. MI0005712, SEQ ID NO: 335) is known to have a hairpin-like structure.
[0264] As used herein, the term “hsa-miR-1915-5p gene” or “hsa-miR-1915-5p” includes the hsa-miR-1915-5p gene described in SEQ ID NO: 149 (miRBase Accession No. MIMAT0007891) and homologs or orthologs in other biological species. The hsa-miR-1915-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of “hsa-miR-1915-5p,” “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 336) is known to have a hairpin-like structure.
[0265] As used herein, the term "hsa-miR-1231 gene" or "hsa-miR-1231" includes the hsa-miR-1231 gene described in SEQ ID NO: 150 (miRBase Accession No. MIMAT0005586) and homologs or orthologs in other species. The hsa-miR-1231 gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1231," "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 337) is known to form a hairpin-like structure.
[0266] As used herein, the term "hsa-miR-663b gene" or "hsa-miR-663b" includes the hsa-miR-663b gene described in SEQ ID NO: 151 (miRBase Accession No. MIMAT0005867) and homologs or orthologs in other species. The hsa-miR-663b gene can be obtained by the method described in Takada S et al., 2008, Leukemia, Vol. 22, pp. 1274-1278. Furthermore, as a precursor of "hsa-miR-663b," "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 338) is known to have a hairpin-like structure.
[0267] As used herein, the term "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" includes the hsa-miR-1225-5p gene described in SEQ ID NO: 152 (miRBase Accession No. MIMAT0005572) and homologs or orthologs in other species. The hsa-miR-1225-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1225-5p", "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 325) is known to have a hairpin-like structure.
[0268] As used herein, the term "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" includes the hsa-miR-4763-3p gene described in SEQ ID NO: 153 (miRBase Accession No. MIMAT0019913) and homologs or orthologs in other species. The hsa-miR-4763-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4763-3p", "hsa-mir-4763" (miRBase Accession No. MI0017404, SEQ ID NO: 339) is known to have a hairpin-like structure.
[0269] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" includes the hsa-miR-3656 gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0018076) and homologs or orthologs in other species. The hsa-miR-3656 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Furthermore, as a precursor of "hsa-miR-3656", "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 340) is known to have a hairpin-like structure.
[0270] As used herein, the term "hsa-miR-4488 gene" or "hsa-miR-4488" includes the hsa-miR-4488 gene described in SEQ ID NO: 155 (miRBase Accession No. MIMAT0019022) and homologs or orthologs in other species. The hsa-miR-4488 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4488", "hsa-mir-4488" (miRBase Accession No. MI0016849, SEQ ID NO: 341) is known to have a hairpin-like structure.
[0271] As used herein, the term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" includes the hsa-miR-125a-3p gene described in SEQ ID NO: 156 (miRBase Accession No. MIMAT0004602) and homologs or orthologs in other biological species. The hsa-miR-125a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-125a-3p", "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 342) is known to have a hairpin-like structure.
[0272] As used herein, the term “hsa-miR-1469 gene” or “hsa-miR-1469” includes the hsa-miR-1469 gene described in SEQ ID NO: 157 (miRBase Accession No. MIMAT0007347) and homologs or orthologs in other biological species. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p157. In addition, as a precursor of “hsa-miR-1469”, “hsa-mir-1469” (miRBase Accession No. MI0007074, SEQ ID NO: 343) that forms a hairpin-like structure is known.
[0273] As used herein, the term "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" includes the hsa-miR-1228-5p gene described in SEQ ID NO: 158 (miRBase Accession No. MIMAT0005582) and homologs or orthologs in other species. The hsa-miR-1228-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1228-5p", "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 344) is known to have a hairpin-like structure.
[0274] As used herein, the term "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" includes the hsa-miR-6798-5p gene described in SEQ ID NO: 159 (miRBase Accession No. MIMAT0027496) and homologs or orthologs in other species. The hsa-miR-6798-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6798-5p", "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 345) is known to have a hairpin-like structure.
[0275] As used herein, the term "hsa-miR-1268b gene" or "hsa-miR-1268b" includes the hsa-miR-1268b gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0018925) and homologs or orthologs in other species. The hsa-miR-1268b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-1268b", "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 346) is known to have a hairpin-like structure.
[0276] As used herein, the term "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" includes the hsa-miR-6732-5p gene described in SEQ ID NO: 161 (miRBase Accession No. MIMAT0027365) and homologs or orthologs in other species. The hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6732-5p," "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 347) is known to have a hairpin-like structure.
[0277] As used herein, the term "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" includes the hsa-miR-1915-3p gene described in SEQ ID NO: 162 (miRBase Accession No. MIMAT0007892) and homologs or orthologs in other biological species. The hsa-miR-1915-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of "hsa-miR-1915-3p", "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 336) is known to have a hairpin-like structure.
[0278] As used herein, the term “hsa-miR-4433b-3p gene” or “hsa-miR-4433b-3p” includes the hsa-miR-4433b-3p gene described in SEQ ID NO: 163 (miRBase Accession No. MIMAT0030414) and homologs or orthologs in other species. The hsa-miR-4433b-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of “hsa-miR-4433b-3p,” “hsa-mir-4433b” (miRBase Accession No. MI0025511, SEQ ID NO: 348) is known to have a hairpin-like structure.
[0279] As used herein, the term “hsa-miR-1207-5p gene” or “hsa-miR-1207-5p” includes the hsa-miR-1207-5p gene described in SEQ ID NO: 164 (miRBase Accession No. MIMAT0005871) and homologs or orthologs in other biological species. The hsa-miR-1207-5p gene can be obtained by the method described in Huppi K et al., 2008, Mol Cancer Res, Vol. 6, pp. 212-221. In addition, as a precursor of “hsa-miR-1207-5p”, “hsa-mir-1207” (miRBase Accession No. MI0006340, SEQ ID NO: 349) is known to have a hairpin-like structure.
[0280] As used herein, the term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" includes the hsa-miR-4433-3p gene described in SEQ ID NO: 165 (miRBase Accession No. MIMAT0018949) and homologs or orthologs in other species. The hsa-miR-4433-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4433-3p", "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 350) is known to have a hairpin-like structure.
[0281] As used herein, the term “hsa-miR-6879-5p gene” or “hsa-miR-6879-5p” includes the hsa-miR-6879-5p gene described in SEQ ID NO: 166 (miRBase Accession No. MIMAT0027658) and homologs or orthologs in other species. The hsa-miR-6879-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6879-5p,” “hsa-mir-6879” (miRBase Accession No. MI0022726, SEQ ID NO: 351) is known to have a hairpin-like structure.
[0282] As used herein, the term "hsa-miR-4417 gene" or "hsa-miR-4417" includes the hsa-miR-4417 gene described in SEQ ID NO: 167 (miRBase Accession No. MIMAT0018929) and homologs or orthologs in other species. The hsa-miR-4417 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4417," "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 352) is known to have a hairpin-like structure.
[0283] As used herein, the term "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" includes the hsa-miR-30c-1-3p gene described in SEQ ID NO: 168 (miRBase Accession No. MIMAT0004674) and homologs or orthologs in other species. The hsa-miR-30c-1-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-30c-1-3p", "hsa-mir-30c-1" (miRBase Accession No. MI0000736, SEQ ID NO: 353) is known to have a hairpin-like structure.
[0284] As used herein, the term "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" includes the hsa-miR-4638-5p gene described in SEQ ID NO: 169 (miRBase Accession No. MIMAT0019695) and homologs or orthologs in other biological species. The hsa-miR-4638-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4638-5p", "hsa-mir-4638" (miRBase Accession No. MI0017265, SEQ ID NO: 354) is known to have a hairpin-like structure.
[0285] As used herein, the term "hsa-miR-6088 gene" or "hsa-miR-6088" includes the hsa-miR-6088 gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0023713) and homologs or orthologs in other species. The hsa-miR-6088 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor of "hsa-miR-6088," "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 355) is known to have a hairpin-like structure.
[0286] As used herein, the term “hsa-miR-4270 gene” or “hsa-miR-4270” includes the hsa-miR-4270 gene described in SEQ ID NO: 171 (miRBase Accession No. MIMAT0016900) and homologs or orthologs in other biological species. The hsa-miR-4270 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4270”, “hsa-mir-4270” (miRBase Accession No. MI0015878, SEQ ID NO: 356) is known to have a hairpin-like structure.
[0287] As used herein, the term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" includes the hsa-miR-6782-5p gene described in SEQ ID NO: 172 (miRBase Accession No. MIMAT0027464) and homologs or orthologs in other species. The hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6782-5p," "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 357) is known to have a hairpin-like structure.
[0288] As used herein, the term "hsa-miR-665 gene" or "hsa-miR-665" includes the hsa-miR-665 gene described in SEQ ID NO: 173 (miRBase Accession No. MIMAT0004952) and homologs or orthologs in other species. The hsa-miR-665 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-665," "hsa-mir-665" (miRBase Accession No. MI0005563, SEQ ID NO: 358) is known to have a hairpin-like structure.
[0289] As used herein, the term "hsa-miR-486-5p gene" or "hsa-miR-486-5p" includes the hsa-miR-486-5p gene described in SEQ ID NO: 174 (miRBase Accession No. MIMAT0002177) and homologs or orthologs in other species. The hsa-miR-486-5p gene can be obtained by the method described in Fu H et al., 2005, FEBS Lett, Vol. 579, pp. 3849-3854. Furthermore, as precursors of "hsa-miR-486-5p", "hsa-mir-486, hsa-mir-486-2" (miRBase Accession Nos. MI0002470, MI0023622, SEQ ID NOs: 323, 324) are known to form hairpin-like structures.
[0290] As used herein, the term "hsa-miR-4655-5p gene" or "hsa-miR-4655-5p" includes the hsa-miR-4655-5p gene described in SEQ ID NO: 175 (miRBase Accession No. MIMAT0019721) and homologs or orthologs in other species. The hsa-miR-4655-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4655-5p", "hsa-mir-4655" (miRBase Accession No. MI0017283, SEQ ID NO: 359) is known to have a hairpin-like structure.
[0291] As used herein, the term “hsa-miR-1275 gene” or “hsa-miR-1275” includes the hsa-miR-1275 gene described in SEQ ID NO: 176 (miRBase Accession No. MIMAT0005929) and homologs or orthologs in other biological species. The hsa-miR-1275 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1275”, “hsa-mir-1275” (miRBase Accession No. MI0006415, SEQ ID NO: 360) is known to have a hairpin-like structure.
[0292] As used herein, the term "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" includes the hsa-miR-6806-5p gene described in SEQ ID NO: 177 (miRBase Accession No. MIMAT0027512) and homologs or orthologs in other species. The hsa-miR-6806-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6806-5p", "hsa-mir-6806" (miRBase Accession No. MI0022651, SEQ ID NO: 361) is known to have a hairpin-like structure.
[0293] As used herein, the term "hsa-miR-614 gene" or "hsa-miR-614" includes the hsa-miR-614 gene described in SEQ ID NO: 178 (miRBase Accession No. MIMAT0003282) and homologs or orthologs in other species. The hsa-miR-614 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, as a precursor of "hsa-miR-614", "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 362) is known to have a hairpin-like structure.
[0294] As used herein, the term "hsa-miR-3937 gene" or "hsa-miR-3937" includes the hsa-miR-3937 gene described in SEQ ID NO: 179 (miRBase Accession No. MIMAT0018352) and homologs or orthologs in other species. The hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3937," "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 363) is known to have a hairpin-like structure.
[0295] As used herein, the term "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" includes the hsa-miR-6752-5p gene described in SEQ ID NO: 180 (miRBase Accession No. MIMAT0027404) and homologs or orthologs in other species. The hsa-miR-6752-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6752-5p," "hsa-mir-6752" (miRBase Accession No. MI0022597, SEQ ID NO: 364) is known to have a hairpin-like structure.
[0296] As used herein, the term "hsa-miR-6771-5p gene" or "hsa-miR-6771-5p" includes the hsa-miR-6771-5p gene described in SEQ ID NO: 181 (miRBase Accession No. MIMAT0027442) and homologs or orthologs in other species. The hsa-miR-6771-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6771-5p", "hsa-mir-6771" (miRBase Accession No. MI0022616, SEQ ID NO: 365) is known to have a hairpin-like structure.
[0297] As used herein, the term "hsa-miR-4450 gene" or "hsa-miR-4450" includes the hsa-miR-4450 gene described in SEQ ID NO: 182 (miRBase Accession No. MIMAT0018971) and homologs or orthologs in other species. The hsa-miR-4450 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4450", "hsa-mir-4450" (miRBase Accession No. MI0016795, SEQ ID NO: 366) is known to have a hairpin-like structure.
[0298] As used herein, the term "hsa-miR-211-3p gene" or "hsa-miR-211-3p" includes the hsa-miR-211-3p gene described in SEQ ID NO: 183 (miRBase Accession No. MIMAT0022694) and homologs or orthologs in other species. The hsa-miR-211-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. Furthermore, as a precursor of "hsa-miR-211-3p", "hsa-mir-211" (miRBase Accession No. MI0000287, SEQ ID NO: 367) is known to have a hairpin-like structure.
[0299] As used herein, the term "hsa-miR-663a gene" or "hsa-miR-663a" includes the hsa-miR-663a gene described in SEQ ID NO: 184 (miRBase Accession No. MIMAT0003326) and homologs or orthologs in other species. The hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-663a", "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 368) is known to have a hairpin-like structure.
[0300] As used herein, the term "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" includes the hsa-miR-6842-5p gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0027586) and homologs or orthologs in other species. The hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6842-5p", "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 369) is known to have a hairpin-like structure.
[0301] As used herein, the term "hsa-miR-7114-5p gene" or "hsa-miR-7114-5p" includes the hsa-miR-7114-5p gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0028125) and homologs or orthologs in other species. The hsa-miR-7114-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7114-5p", "hsa-mir-7114" (miRBase Accession No. MI0022965, SEQ ID NO: 370) is known to have a hairpin-like structure.
[0302] As used herein, the term "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" includes the hsa-miR-6779-5p gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0027458) and homologs or orthologs in other species. The hsa-miR-6779-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6779-5p", "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 371) is known to have a hairpin-like structure.
[0303] As used herein, the term "hsa-miR-204-3p gene" or "hsa-miR-204-3p" includes the hsa-miR-204-3p gene described in SEQ ID NO: 580 (miRBase Accession No. MIMAT0022693) and homologs or orthologs in other species. The hsa-miR-204-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. Furthermore, as a precursor of "hsa-miR-204-3p", "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 612) is known, which has a hairpin-like structure.
[0304] As used herein, the term "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" includes the hsa-miR-642a-3p gene described in SEQ ID NO: 581 (miRBase Accession No. MIMAT0020924) and homologs or orthologs in other species. The hsa-miR-642a-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-642a-3p", "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 613) is known to have a hairpin-like structure.
[0305] As used herein, the term "hsa-miR-762 gene" or "hsa-miR-762" includes the hsa-miR-762 gene described in SEQ ID NO: 582 (miRBase Accession No. MIMAT0010313) and homologs or orthologs in other species. The hsa-miR-762 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. In addition, as a precursor of "hsa-miR-762", "hsa-mir-762" (miRBase Accession No. MI0003892, SEQ ID NO: 614) is known to have a hairpin-like structure.
[0306] As used herein, the term "hsa-miR-1202 gene" or "hsa-miR-1202" includes the hsa-miR-1202 gene described in SEQ ID NO: 583 (miRBase Accession No. MIMAT0005865) and homologs or orthologs in other species. The hsa-miR-1202 gene can be obtained by the method described in Marton S et al., 2008, Leukemia, Vol. 22, pp. 330-338. Furthermore, as a precursor of "hsa-miR-1202," "hsa-mir-1202" (miRBase Accession No. MI0006334, SEQ ID NO: 615) is known to have a hairpin-like structure.
[0307] As used herein, the term "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" includes the hsa-miR-3162-5p gene described in SEQ ID NO: 584 (miRBase Accession No. MIMAT0015036) and homologs or orthologs in other species. The hsa-miR-3162-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., Vol. 5, e9685. Furthermore, as a precursor of "hsa-miR-3162-5p", "hsa-mir-3162" (miRBase Accession No. MI0014192, SEQ ID NO: 616) is known to have a hairpin-like structure.
[0308] As used herein, the term “hsa-miR-3196 gene” or “hsa-miR-3196” includes the hsa-miR-3196 gene described in SEQ ID NO: 585 (miRBase Accession No. MIMAT0015080) and homologs or orthologs in other species. The hsa-miR-3196 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3196,” “hsa-mir-3196” (miRBase Accession No. MI0014241, SEQ ID NO: 617) is known to have a hairpin-like structure.
[0309] As used herein, the term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" includes the hsa-miR-3622a-5p gene described in SEQ ID NO: 586 (miRBase Accession No. MIMAT0018003) and homologs or orthologs in other species. The hsa-miR-3622a-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., Vol. 8, p58. Furthermore, as a precursor of "hsa-miR-3622a-5p," "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 618) is known to have a hairpin-like structure.
[0310] As used herein, the term "hsa-miR-3665 gene" or "hsa-miR-3665" includes the hsa-miR-3665 gene described in SEQ ID NO: 587 (miRBase Accession No. MIMAT0018087) and homologs or orthologs in other species. The hsa-miR-3665 gene can be obtained by the method described in Xie X et al., 2005, Nature, Vol. 434, pp. 338-345. Furthermore, as a precursor of "hsa-miR-3665," "hsa-mir-3665" (miRBase Accession No. MI0016066, SEQ ID NO: 619) is known to have a hairpin-like structure.
[0311] As used herein, the term "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" includes the hsa-miR-3940-5p gene described in SEQ ID NO: 588 (miRBase Accession No. MIMAT0019229) and homologs or orthologs in other species. The hsa-miR-3940-5p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3940-5p," "hsa-mir-3940" (miRBase Accession No. MI0016597, SEQ ID NO: 620) is known to have a hairpin-like structure.
[0312] As used herein, the term “hsa-miR-4294 gene” or “hsa-miR-4294” includes the hsa-miR-4294 gene described in SEQ ID NO: 589 (miRBase Accession No. MIMAT0016849) and homologs or orthologs in other species. The hsa-miR-4294 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4294,” “hsa-mir-4294” (miRBase Accession No. MI0015827, SEQ ID NO: 621) is known to have a hairpin-like structure.
[0313] As used herein, the term "hsa-miR-4466 gene" or "hsa-miR-4466" includes the hsa-miR-4466 gene described in SEQ ID NO: 590 (miRBase Accession No. MIMAT0018993) and homologs or orthologs in other species. The hsa-miR-4466 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4466", "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 622) is known to have a hairpin-like structure.
[0314] As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" includes the hsa-miR-4476 gene described in SEQ ID NO: 591 (miRBase Accession No. MIMAT0019003) and homologs or orthologs in other species. The hsa-miR-4476 gene can be obtained by the method described in Jima DD et al., 2010, Blood., Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4476", "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 623) is known to have a hairpin-like structure.
[0315] As used herein, the term "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" includes the hsa-miR-4723-5p gene described in SEQ ID NO: 592 (miRBase Accession No. MIMAT0019838) and homologs or orthologs in other species. The hsa-miR-4723-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4723-5p", "hsa-mir-4723" (miRBase Accession No. MI0017359, SEQ ID NO: 624) is known to have a hairpin-like structure.
[0316] As used herein, the term "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" includes the hsa-miR-4725-3p gene described in SEQ ID NO: 593 (miRBase Accession No. MIMAT0019844) and homologs or orthologs in other species. The hsa-miR-4725-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4725-3p", "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 625) is known to have a hairpin-like structure.
[0317] As used herein, the term "hsa-miR-4730 gene" or "hsa-miR-4730" includes the hsa-miR-4730 gene described in SEQ ID NO: 594 (miRBase Accession No. MIMAT0019852) and homologs or orthologs in other species. The hsa-miR-4730 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4730", "hsa-mir-4730" (miRBase Accession No. MI0017367, SEQ ID NO: 626) is known to have a hairpin-like structure.
[0318] As used herein, the term "hsa-miR-4739 gene" or "hsa-miR-4739" includes the hsa-miR-4739 gene described in SEQ ID NO: 595 (miRBase Accession No. MIMAT0019868) and homologs or orthologs in other species. The hsa-miR-4739 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4739," "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 627) is known to have a hairpin-like structure.
[0319] As used herein, the term "hsa-miR-4787-5p gene" or "hsa-miR-4787-5p" includes the hsa-miR-4787-5p gene described in SEQ ID NO: 596 (miRBase Accession No. MIMAT0019956) and homologs or orthologs in other species. The hsa-miR-4787-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4787-5p", "hsa-mir-4787" (miRBase Accession No. MI0017434, SEQ ID NO: 628) is known to have a hairpin-like structure.
[0320] As used herein, the term “hsa-miR-5787 gene” or “hsa-miR-5787” includes the hsa-miR-5787 gene described in SEQ ID NO: 597 (miRBase Accession No. MIMAT0023252) and homologs or orthologs in other species. The hsa-miR-5787 gene can be obtained by the method described in Yoo H et al., 2011, Biochem Biophys Res Commun, Vol. 415, pp. 567-572. Furthermore, as a precursor of “hsa-miR-5787,” “hsa-mir-5787” (miRBase Accession No. MI0019797, SEQ ID NO: 629) is known to have a hairpin-like structure.
[0321] As used herein, the term "hsa-miR-6085 gene" or "hsa-miR-6085" includes the hsa-miR-6085 gene described in SEQ ID NO: 598 (miRBase Accession No. MIMAT0023710) and homologs or orthologs in other species. The hsa-miR-6085 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA., Vol. 18, pp. 472-484. Furthermore, as a precursor of "hsa-miR-6085," "hsa-mir-6085" (miRBase Accession No. MI0020362, SEQ ID NO: 630) is known to have a hairpin-like structure.
[0322] As used herein, the term "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" includes the hsa-miR-6717-5p gene described in SEQ ID NO: 599 (miRBase Accession No. MIMAT0025846) and homologs or orthologs in other species. The hsa-miR-6717-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6717-5p," "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 631) is known to have a hairpin-like structure.
[0323] As used herein, the term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" includes the hsa-miR-6724-5p gene described in SEQ ID NO: 600 (miRBase Accession No. MIMAT0025856) and homologs or orthologs in other species. The hsa-miR-6724-5p gene can be obtained by the method described in Li Y et al., 2012, Gene., Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6724-5p," "hsa-mir-6724" (miRBase Accession No. MI0022559, SEQ ID NO: 632) is known to have a hairpin-like structure.
[0324] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" includes the hsa-miR-6777-5p gene described in SEQ ID NO: 601 (miRBase Accession No. MIMAT0027454) and homologs or orthologs in other species. The hsa-miR-6777-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6777-5p," "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 633) is known to have a hairpin-like structure.
[0325] As used herein, the term "hsa-miR-6778-5p gene" or "hsa-miR-6778-5p" includes the hsa-miR-6778-5p gene described in SEQ ID NO: 602 (miRBase Accession No. MIMAT0027456) and homologs or orthologs in other species. The hsa-miR-6778-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6778-5p", "hsa-mir-6778" (miRBase Accession No. MI0022623, SEQ ID NO: 634) is known to have a hairpin-like structure.
[0326] As used herein, the term "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" includes the hsa-miR-6787-5p gene described in SEQ ID NO: 603 (miRBase Accession No. MIMAT0027474) and homologs or orthologs in other species. The hsa-miR-6787-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6787-5p," "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 635) is known to have a hairpin-like structure.
[0327] As used herein, the term "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" includes the hsa-miR-6789-5p gene described in SEQ ID NO: 604 (miRBase Accession No. MIMAT0027478) and homologs or orthologs in other species. The hsa-miR-6789-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6789-5p," "hsa-mir-6789" (miRBase Accession No. MI0022634, SEQ ID NO: 636) is known to have a hairpin-like structure.
[0328] As used herein, the term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" includes the hsa-miR-6845-5p gene described in SEQ ID NO: 605 (miRBase Accession No. MIMAT0027590) and homologs or orthologs in other species. The hsa-miR-6845-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6845-5p," "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 637) is known to have a hairpin-like structure.
[0329] As used herein, the term "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" includes the hsa-miR-6893-5p gene described in SEQ ID NO: 606 (miRBase Accession No. MIMAT0027686) and homologs or orthologs in other species. The hsa-miR-6893-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6893-5p," "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 638) is known to have a hairpin-like structure.
[0330] As used herein, the term "hsa-miR-16-5p gene" or "hsa-miR-16-5p" includes the hsa-miR-16-5p gene described in SEQ ID NO: 607 (miRBase Accession No. MIMAT0000069) and homologs or orthologs in other biological species. The hsa-miR-16-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol., Vol. 12, pp. 735-739. Furthermore, as precursors of "hsa-miR-16-5p," "hsa-mir-16-1 and hsa-mir-16-2" (miRBase Accession Nos. MI0000070 and MI0000115, SEQ ID NOs: 639 and 640) are known to form hairpin-like structures.
[0331] As used herein, the term "hsa-miR-423-5p gene" or "hsa-miR-423-5p" includes the hsa-miR-423-5p gene described in SEQ ID NO: 608 (miRBase Accession No. MIMAT0004748) and homologs or orthologs in other biological species. The hsa-miR-423-5p gene can be obtained by the method described in Kasashima K et al., 2004, Biochem Biophys Res Commun., Vol. 322, pp. 403-410. In addition, as a precursor of "hsa-miR-423-5p", "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 641) is known to have a hairpin-like structure.
[0332] As used herein, the term "hsa-miR-451a gene" or "hsa-miR-451a" includes the hsa-miR-451a gene described in SEQ ID NO: 609 (miRBase Accession No. MIMAT0001631) and homologs or orthologs in other species. The hsa-miR-451a gene can be obtained by the method described in Altuvia Y et al., 2005, Nucleic Acids Res., Vol. 33, pp. 2697-2706. Furthermore, as a precursor of "hsa-miR-451a," "hsa-mir-451a" (miRBase Accession No. MI0001729, SEQ ID NO: 642) is known to have a hairpin-like structure.
[0333] As used herein, the term "hsa-miR-564 gene" or "hsa-miR-564" includes the hsa-miR-564 gene described in SEQ ID NO: 610 (miRBase Accession No. MIMAT0003228) and homologs or orthologs in other species. The hsa-miR-564 gene can be obtained by the method described in Cummins JM, 2006, Proc Natl Acad Sci, Vol. 103, p3687-3692. In addition, as a precursor of "hsa-miR-564", "hsa-mir-564" (miRBase Accession No. MI0003570, SEQ ID NO: 643) is known to have a hairpin-like structure.
[0334] As used herein, the term "hsa-miR-671-5p gene" or "hsa-miR-671-5p" includes the hsa-miR-671-5p gene described in SEQ ID NO: 611 (miRBase Accession No. MIMAT0003880) and homologs or orthologs in other species. The hsa-miR-671-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-671-5p", "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 644) is known to have a hairpin-like structure.
[0335] In addition, when a mature miRNA is cut out from an RNA precursor that forms a hairpin-like structure as a mature miRNA, sometimes one to several bases before and after the sequence are cut out short, or cut out long, and base substitution occurs to become a mutant, which is called isomiR (Morin RD. et al., 2008, Genome Res., Vol. 18, p. 610-621). In miRBase version 20, in addition to the base sequences shown in any one of sequence numbers 1 to 187 and 580 to 611, multiple mutants and fragments of the base sequences shown in any one of sequence numbers 372 to 579 and 645 to 684, which are called isomiR, are also shown. These mutants can also be obtained as miRNAs with base sequences shown in any one of sequence numbers 1 to 187 and 580 to 611. That is, the serial numbers 1, 2, 4, 5, 6, 7, 10, 12, 15, 16, 18, 19, 21, 22, 24, 25, 27, 30, 31, 33, 34, 36, 39, 41, 42, 43, 44, 45, 46, 48, 51, 53, 58, 61, 62, 63, 66, 69, 73, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 6, 77, 78, 83, 84, 85, 86, 87, 88, 90, 94, 95, 96, 98, 100, 102, 103, 104, 105, 106, 107, 108, 109, 111, 115, 117, 119, 120, 123, 124, 125, 126, 127, 128, 131, 1 36, 137, 139, 140, 143, 144, 147, 149, 151, 153, 154, 155, 156, 158, 160, 162, 165, 167, 168, 169, 170, 173, 174, 175, 176, 178, 182, 183, 184, 580, 581, 584, 585, 587, 588, 590, 591, 592, 593, 594, 595, 597, 599, 600, 607, 608, 609 and 611, or a polynucleotide consisting of a base sequence in which u is t in the base sequence, as, for example, the longest variant registered in miRBase version 20,Serial numbers 372, 374, 376, 378, 380, 382, 384, 386, 388, 390, 392, 394, 396, 398, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 4 0, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 4 94, 496, 498, 500, 502, 504, 506, 508, 510, 512, 514, 516, 518, 520, 522, 524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550, 552, 554, 556, The polynucleotides shown in 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578, 645, 647, 650, 652, 655, 657, 659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681 and 683. In addition, the serial numbers 1, 2, 4, 5, 6, 7, 10, 12, 15, 16, 18, 19, 21, 22, 24, 25, 27, 30, 31, 33, 34, 36, 39, 41, 42, 43, 44, 45, 46, 48, 51, 53, 58, 61, 62, 63, 66, 69, 73, 75, 76, 77, 78, 83, 84, 85, 86, 87, 88, 90, 94, 95, 96, 98, 100, 102, 103, 104, 105, 106, 107, 108, 109, 111, 115, 117, 119, 120, 123, 124, 125, 126, 127 , 128, 131, 136, 137, 139, 140, 143, 144, 147, 149, 151, 153, 154, 155, 156, 158, 160, 162, 165, 167, 168, 169, 170, 173, 174, 175, 176, 178, 182, 183, 184, 580, 581, 583, 584, 585, 586, 587, 588, 590, 591, 592, 593, 594, 595, 597, 599, 600, 607, 608, 609 and 611, or a variant of a polynucleotide consisting of a base sequence in which u is t in the base sequence,For example, the shortest mutants registered in miRBase version 20 include sequence numbers 373, 375, 377, 379, 381, 383, 385, 387, 389, 391, 393, 395, 397, 399, 401, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 481, 482, 483, 484, 485, 486, 487, 23, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, 489, 4 91, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545, 547, 549, 551, 553, 555, 557, 5 59, 561, 563, 565, 567, 569, 571, 573, 575, 577, 579, 646, 648, 649, 651, 653, 654, 656, 658, 660, 662, 664, 666, 668, 670, 672, 674, 676, 678, 680, 682, and 684. In addition to these mutants and fragments, polynucleotides of multiple isomiRs registered in miRBase as sequence numbers 1 to 187 and 580 to 611 can be cited. Further, as examples of polynucleotides comprising the base sequence represented by any one of sequence numbers 1 to 187 and 580 to 611, the polynucleotides represented by any one of sequence numbers 188 to 371 and 612 to 644 as precursors can be cited, respectively.
[0336] Table 1 lists the names and miRBase accession numbers (accession numbers) of the genes represented by SEQ ID NOs: 1 to 684.
[0337] In this specification, "capable of specifically binding" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to other nucleic acids.
[0338] [Table 1]
[0339]
[0340]
[0341]
[0342]
[0343]
[0344]
[0345]
[0346]
[0347]
[0348]
[0349]
[0350]
[0351]
[0352]
[0353]
[0354]
[0355]
[0356] This application claims the benefit of priority from Japanese Patent Application No. 2014-121377 filed on June 12, 2014 and Japanese Patent Application No. 2015-71756 filed on March 31, 2015, and includes the contents disclosed in the specifications of those patent applications.
[0357] Effects of the Invention
[0358] By means of the present invention, prostate cancer can be detected easily and with high accuracy.
[0359] For example, using the measured values of several miRNAs in the patient's blood, serum, or plasma, which can be collected minimally invasively, as indicators, it is possible to easily detect whether the patient has prostate cancer. BRIEF DESCRIPTION OF THE DRAWINGS
[0361] Figure 1 The figure shows the relationship between the base sequences of hsa-miR-1343-3p shown in sequence number 7 and hsa-miR-1343-5p shown in sequence number 9, which are generated from hsa-mir-1343 shown in sequence number 194 as a precursor.
[0362] Figure 2Middle left figure: A graph showing the measured values of hsa-miR-4443 (sequence number 1) of healthy subjects (100 people) and prostate cancer patients (35 people) selected as the learning sample group as the vertical axis. The horizontal line in the figure represents the threshold value (6.84) for distinguishing the two groups optimized by Fisher's discriminant analysis. Right figure: A graph showing the measured values of hsa-miR-4443 (sequence number 1) of healthy subjects (50 people) and prostate cancer patients (17 people) selected as the test sample group as the vertical axis. The horizontal line in the figure represents the threshold value (6.84) for distinguishing the two groups set by the learning sample group.
[0363] Figure 3 Middle left figure: A graph showing the measured values of hsa-miR-4443 (sequence number 1) of healthy subjects (100 people, circles) and prostate cancer patients (35 people, triangles) selected as the learning sample group as the horizontal axis and the measured values of hsa-miR-1908-5p (sequence number 2) as the vertical axis. The line in the figure represents the discriminant function (0 = 1.15x + y + 19.53) for distinguishing the two groups, which was optimized by Fisher's discriminant analysis. Right figure: A graph showing the measured values of hsa-miR-4443 (sequence number 1) of healthy subjects (50 people, circles) and prostate cancer patients (17 people, triangles) selected as the test sample group as the horizontal axis and the measured values of hsa-miR-1908-5p (sequence number 2) as the vertical axis. The line in the figure represents the threshold value (0 = 1.15x + y + 19.53) for distinguishing the two groups, which was set by the learning sample group.
[0364] Figure 4Upper middle figure: Measured values for hsa-miR-4745-5p (SEQ ID NO: 12), hsa-miR-92a-2-5p (SEQ ID NO: 16), hsa-miR-6820-5p (SEQ ID NO: 135), and hsa-miR-125a-3p (SEQ ID NO: 156) were obtained from 35 prostate cancer patients, 99 healthy controls, and 63 breast cancer patients selected as a learning sample group. Fisher's discriminant analysis was used to create a discriminant equation (1.34 x miR-92a-2-5p + 1.56 x miR-6820-5p - 1.29 x miR-4745-5p - 0.76 x miR-125a-3p - 4.31). The graph shows the discriminant score obtained from this discriminant equation on the vertical axis and the sample group on the horizontal axis. The dotted line in the figure indicates the discriminant boundary between the two groups, where the discriminant score is 0. Bottom figure: Measured values for hsa-miR-4745-5p (SEQ ID NO: 12), hsa-miR-92a-2-5p (SEQ ID NO: 16), hsa-miR-6820-5p (SEQ ID NO: 135), and hsa-miR-125a-3p (SEQ ID NO: 156) from 17 prostate cancer patients, 51 healthy controls, and 30 breast cancer patients selected as the test sample group, with the discriminant score obtained using the discriminant formula developed for the learning sample group as the vertical axis and the sample group as the horizontal axis. The dotted line in the figure represents the discriminant boundary between the two groups, where the discriminant score is 0. DETAILED DESCRIPTION
[0365] The present invention will be described in further detail below.
[0366] 1. Prostate cancer target nucleic acid
[0367] The nucleic acid probe or primer for detecting prostate cancer as defined above of the present invention is used to detect the presence and / or absence of prostate cancer or prostate cancer cells, and the main target nucleic acid as a prostate cancer marker comprises hsa-miR-4443, hsa-miR-1908-5p, hsa-miR-4257, hsa-miR-3197, hsa-miR-3188, hsa-miR-4649-5p, hsa-miR-1343-3p, hsa-miR-6861-5p, hsa-miR-1343-5p, hsa-miR-642b-3p, hsa-miR-6741-5p, hsa-miR-4745 -5p, hsa-miR-6826-5p, hsa-miR-3663-3p, hsa-miR-3131, hsa-miR-92a-2-5p, hsa-miR-4258, hsa-miR-4448, hsa-miR-6125, hsa-miR-6880-5p, hsa- miR-6132, hsa-miR-4467, hsa-miR-6749-5p, hsa-miR-2392, hsa-miR-1273g-3p, hsa-miR-4746-3p, hsa-miR-1914-3p, hsa-miR-7845-5p, hsa-miR-6 726-5p, hsa-miR-128-2-5p, hsa-miR-4651, hsa-miR-6765-3p, hsa-miR-3185, hsa-miR-4792, hsa-miR-6887-5p, hsa-miR-5572, hsa-miR-3619-3p, hsa-miR-6780b-5p, hsa-miR-4707-5p, hsa-miR-8063, hsa-miR-4454, hsa-miR-4525, hsa-miR-7975, hsa-miR-744-5p, hsa-miR-3135b, hsa-miR-464 8. hsa-miR-6816-5p, hsa-miR-4741, hsa-miR-7150, hsa-miR-6791-5p, hsa-miR-1247-3p, hsa-miR-7977, hsa-miR-4497, hsa-miR-6090, hsa-miR-67 81-5p, hsa-miR-6870-5p, hsa-miR-6729-5p, hsa-miR-4530, hsa-miR-7847-3p, hsa-miR-6825-5p, hsa-miR-4674, hsa-miR-3917, hsa-miR-4707-3p,hsa-miR-6885-5p, hsa-miR-6722-3p, hsa-miR-4516, hsa-miR-6757-5p, hsa-miR-6840-3p, hsa-miR-5195-3p, hsa-miR-6756-5p, hsa-miR-6800-5p hsa-miR-6727-5p, hsa-miR-6126, hsa-miR-6872-3p, hsa-miR-4446-3p, hsa-miR-1268a, hsa-miR-1908-3p, hsa-miR-3679-5p, hsa-miR-4534, hsa-m iR-4675, hsa-miR-7108-5p, hsa-miR-6799-5p, hsa-miR-4695-5p, hsa-miR-3178, hsa-miR-5090, hsa-miR-3180, hsa-miR-1237-5p, hsa-miR-4758-5 p、hsa-miR-3184-5p、hsa-miR-4286、hsa-miR-6784-5p、hsa-miR-6768-5p、hsa-miR-6785-5p、hsa-miR-4706、hsa-miR-711、hsa-miR-1260a、hsa-miR -6746-5p、hsa-miR-6089、hsa-miR-6821-5p、hsa-miR-4667-5p、hsa-miR-8069、hsa-miR-4726-5p、hsa-miR-6124、hsa-miR-4532、hsa-miR-4486、hsa -miR-4728-5p、hsa-miR-4508、hsa-miR-128-1-5p、hsa-miR-4513、hsa-miR-6795-5p、hsa-miR-4689、hsa-miR-6763-5p、hsa-miR-8072、hsa-miR-676 5-5p、hsa-miR-4419b、hsa-miR-7641、hsa-miR-3928-3p、hsa-miR-1227-5p、hsa-miR-4492、hsa-miR-296-3p、hsa-miR-6769a-5p、hsa-miR-6889-5p、 hsa-miR-4632-5p, hsa-miR-4505, hsa-miR-3154, hsa-miR-3648, hsa-miR-4442, hsa-miR-3141, hsa-miR-7113-3p, hsa-miR-6819-5p, hsa-miR-3195hsa-miR-1199-5p, hsa-miR-6738-5p, hsa-miR-4656, hsa-miR-6820-5p, hsa-miR-204-3p, hsa-miR-642a-3p, hsa-miR-762, hsa-miR-1202, h sa-miR-3162-5p, hsa-miR-3196, hsa-miR-3622a-5p, hsa-miR-3665, hsa-miR-3940-5p, hsa-miR-4294, hsa-miR-4466, hsa-miR-4476, hsa-m iR-4723-5p, hsa-miR-4725-3p, hsa-miR-4730, hsa-miR-4739, hsa-miR-4787-5p, hsa-miR-5787, hsa-miR-6085, hsa-miR-6717-5p, hsa-miR At least one of -6724-5p, hsa-miR-6777-5p, hsa-miR-6778-5p, hsa-miR-6787-5p, hsa-miR-6789-5p, hsa-miR-6845-5p and hsa-miR-6893-5p. Other prostate cancer markers that can be further combined with these miRNAs include hsa-miR-615-5p, hsa-miR-486-3p, hsa-miR-1225-3p, hsa-miR-760, hsa-miR-187-5p, hsa-miR-1203, hsa-miR-7110-5p, hsa-miR-371a-5p, hsa-miR-939-5p, hsa-miR-575, hsa-miR-9 At least one of the miRNAs selected from hsa-miR-2b-5p, hsa-miR-887-3p, hsa-miR-920, hsa-miR-1915-5p, hsa-miR-1231, hsa-miR-663b, hsa-miR-1225-5p, hsa-miR-16-5p, hsa-miR-423-5p, hsa-miR-451a, hsa-miR-564, and hsa-miR-671-5p can also be preferably used as the target nucleic acid. Other prostate cancer markers that can be combined with these miRNAs include hsa-miR-4763-3p, hsa-miR-3656, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-1469, hsa-miR-1228-5p, hsa-miR-6798-5p, hsa-miR-1268b,hsa-miR-6732-5p, hsa-miR-1915-3p, hsa-miR-4433b-3p, hsa-miR-1207-5p, hsa-miR-4433-3p, hsa-miR-6879-5p, hsa-miR-44 17. hsa-miR-30c-1-3p, hsa-miR-4638-5p, hsa-miR-6088, hsa-miR-4270, hsa-miR-6782-5p, hsa-miR-665, hsa-miR-486-5p, hs At least one miRNA selected from the group consisting of hsa-miR-4655-5p, hsa-miR-1275, hsa-miR-6806-5p, hsa-miR-614, hsa-miR-3937, hsa-miR-6752-5p, hsa-miR-6771-5p, hsa-miR-4450, hsa-miR-211-3p, hsa-miR-663a, hsa-miR-6842-5p, hsa-miR-7114-5p, and hsa-miR-6779-5p can also be preferably used as the target nucleic acid.
[0368] Among the above-mentioned miRNAs, there are human genes containing the base sequences shown in any one of, for example, SEQ ID NOs: 1 to 187 and 580 to 611 (i.e., hsa-miR-4443, hsa-miR-1908-5p, hsa-miR-4257, hsa-miR-3197, hsa-miR-3188, hsa-miR-4649-5p, hsa-miR-1343-3p, hsa-miR-6861-5p, hsa-miR-1343-5p, hsa-miR-642b-3p, hsa-miR-6741-5p, hsa-miR-4745-5p, hsa-miR-6826-5p, hsa-miR-3663-3p, hsa-miR-3131, hsa-miR-92a-2-5p, hsa-miR-4258, hsa-miR-4448, hsa-miR-6125, hsa-miR-6880-5p, hsa-miR-6132, hsa-miR-4467, hsa-miR-6749-5p, hsa-miR-2392, hsa-miR-1273g-3p, hsa-miR-4746-3p, hsa-miR-1914-3p, hsa-miR-7845-5p, hsa-miR-6726-5p, hsa-miR-128-2-5p, hsa-miR-4651, hsa-miR-6765-3p, hsa-miR-3185, hsa-miR-4792, hsa-miR-6887-5p, hsa-miR-5572, hsa-miR-3619-3p, hsa-miR-6780b-5p, hsa-miR-4707-5p, hsa-miR-8063, hsa-miR-4454, hsa-miR-4525, hsa-miR-7975, hsa-miR-744-5p, hsa-miR-3135b, hsa-miR-4648, hsa-miR-6816-5p, hsa-miR-4741, hsa-miR-7150, hsa-miR-6791-5p, hsa-miR-1247-3p, hsa-miR-7977, hsa-miR-4497, hsa-miR-6090, hsa-miR-6781-5p, hsa-miR-6870-5p, hsa-miR-6729-5p, hsa-miR-4530, hsa-miR-7847-3p, hsa-miR-6825-5p, hsa-miR-4674, hsa-miR-3917, hsa-miR-4707-3p, hsa-miR-6885-5p,hsa-miR-6722-3p, hsa-miR-4516, hsa-miR-6757-5p, hsa-miR-6840-3p, hsa-miR-5195-3p, hsa-miR-6756-5p, hsa-miR-6800-5p, hsa-miR-6727-5p hsa-miR-6126, hsa-miR-6872-3p, hsa-miR-4446-3p, hsa-miR-1268a, hsa-miR-1908-3p, hsa-miR-3679-5p, hsa-miR-4534, hsa-miR-4675, hsa-miR- 7108-5p, hsa-miR-6799-5p, hsa-miR-4695-5p, hsa-miR-3178, hsa-miR-5090, hsa-miR-3180, hsa-miR-1237-5p, hsa-miR-4758-5p, hsa-miR-3184-5 p、hsa-miR-4286、hsa-miR-6784-5p、hsa-miR-6768-5p、hsa-miR-6785-5p、hsa-miR-4706、hsa-miR-711、hsa-miR-1260a、hsa-miR-6746-5p、hsa-miR -6089、hsa-miR-6821-5p、hsa-miR-4667-5p、hsa-miR-8069、hsa-miR-4726-5p、hsa-miR-6124、hsa-miR-4532、hsa-miR-4486、hsa-miR-4728-5p、hsa -miR-4508, hsa-miR-128-1-5p, hsa-miR-4513, hsa-miR-6795-5p, hsa-miR-4689, hsa-miR-6763-5p, hsa-miR-8072, hsa-miR-6765-5p, hsa-miR-441 9b, hsa-miR-7641, hsa-miR-3928-3p, hsa-miR-1227-5p, hsa-miR-4492, hsa-miR-296-3p, hsa-miR-6769a-5p, hsa-miR-6889-5p, hsa-miR-4632-5p hsa-miR-4505, hsa-miR-3154, hsa-miR-3648, hsa-miR-4442, hsa-miR-3141, hsa-miR-7113-3p, hsa-miR-6819-5p, hsa-miR-3195, hsa-miR-1199-5phsa-miR-6738-5p, hsa-miR-4656, hsa-miR-6820-5p, hsa-miR-204-3p, hsa-miR-642a-3p, hsa-miR-762, hsa-miR-1202, hsa-miR-3162-5p, hsa-miR-3196, hsa-miR-3622a-5p, hsa-miR-3665, hsa-miR-3940-5p, hsa-miR-4294, hsa-miR-4466, hsa-miR-4476, hsa-miR-4723-5p, hsa-miR-4725-3p, hsa-miR-4730, hsa-miR-4739, hsa-miR-4787-5p, hsa-miR-5787, hsa-miR-6085, hsa-miR-6717-5p, hsa-miR-6724-5p, hsa-miR-6777-5p, hsa-miR-6778-5p, hsa-miR-6787-5p, hsa-miR-6789-5p, hsa-miR-6845-5p and hsa-miR-6893-5p, hsa-miR-615-5p, hsa-miR-486-3p, hsa-miR-1225-3p, hsa-miR-760, hsa-miR-187-5p, hsa-miR-1203, hsa-miR-7110-5p, hsa-miR-371a-5p, hsa-miR-939-5p, hsa-miR-575, hsa-miR-92b-5p, hsa-miR-887-3p, hsa-miR-920, hsa-miR-1915-5p, hsa-miR-1231, hsa-miR-663b, hsa-miR-1225-5p, hsa-miR-16-5p, hsa-miR-423-5p, hsa-miR-451a, hsa-miR-564 and hsa-miR-671-5p, hsa-miR-4763-3p, hsa-miR-3656, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-1469, hsa-miR-1228-5p, hsa-miR-6798-5p, hsa-miR-1268b, hsa-miR-6732-5p, hsa-miR-1915-3p, hsa-miR-4433b-3p, hsa-miR-1207-5p, hsa-miR-4433-3p, hsa-miR-6879-5p, hsa-miR-4417, hsa-miR-30c-1-3phsa-miR-4638-5p, hsa-miR-6088, hsa-miR-4270, hsa-miR-6782-5p, hsa-miR-665, hsa- miR-486-5p, hsa-miR-4655-5p, hsa-miR-1275, hsa-miR-6806-5p, hsa-miR-614, hsa-miR -3937, hsa-miR-6752-5p, hsa-miR-6771-5p, hsa-miR-4450, hsa-miR-211-3p, hsa-miR-663a, hsa-miR-6842-5p, hsa-miR-7114-5p, and hsa-miR-6779-5p), their homologs, their transcription products, and their mutants or derivatives. Here, genes, homologs, transcription products, mutants, and derivatives are as defined above.
[0369] A preferred target nucleic acid is a human gene comprising the base sequence shown in any one of SEQ ID NOs: 1 to 684, or a transcription product thereof, more preferably the transcription product, ie, miRNA, or its precursor RNA, pri-miRNA or pre-miRNA.
[0370] The first target gene is the hsa-miR-4443 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0371] The second target gene is the hsa-miR-1908-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0372] The third target gene is the hsa-miR-4257 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0373] The fourth target gene is the hsa-miR-3197 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0374] The fifth target gene is the hsa-miR-3188 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0375] The sixth target gene is the hsa-miR-4649-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0376] The seventh target gene is the hsa-miR-1343-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0377] The eighth target gene is the hsa-miR-6861-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0378] The ninth target gene is the hsa-miR-1343-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0379] The tenth target gene is the hsa-miR-642b-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0380] The eleventh target gene is the hsa-miR-6741-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0381] The twelfth target gene is the hsa-miR-4745-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0382] The 13th target gene is the hsa-miR-6826-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0383] The 14th target gene is the hsa-miR-3663-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0384] The fifteenth target gene is the hsa-miR-3131 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0385] The 16th target gene is the hsa-miR-92a-2-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0386] The 17th target gene is the hsa-miR-4258 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0387] The 18th target gene is the hsa-miR-4448 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0388] The 19th target gene is the hsa-miR-6125 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0389] The 20th target gene is the hsa-miR-6880-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0390] The 21st target gene is the hsa-miR-6132 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0391] The 22nd target gene is the hsa-miR-4467 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0392] The 23rd target gene is the hsa-miR-6749-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0393] The 24th target gene is the hsa-miR-2392 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0394] The 25th target gene is the hsa-miR-1273g-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0395] The 26th target gene is the hsa-miR-4746-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0396] The 27th target gene is the hsa-miR-1914-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0397] The 28th target gene is the hsa-miR-7845-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0398] The 29th target gene is the hsa-miR-6726-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0399] The 30th target gene is the hsa-miR-128-2-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0400] The 31st target gene is the hsa-miR-4651 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0401] The 32nd target gene is the hsa-miR-6765-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0402] The 33rd target gene is the hsa-miR-3185 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0403] The 34th target gene is the hsa-miR-4792 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0404] The 35th target gene is the hsa-miR-6887-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0405] The 36th target gene is the hsa-miR-5572 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0406] The 37th target gene is the hsa-miR-3619-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0407] The 38th target gene is the hsa-miR-6780b-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0408] The 39th target gene is the hsa-miR-4707-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0409] The 40th target gene is the hsa-miR-8063 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0410] The 41st target gene is the hsa-miR-4454 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0411] The 42nd target gene is the hsa-miR-4525 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0412] The 43rd target gene is the hsa-miR-7975 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0413] The 44th target gene is the hsa-miR-744-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0414] The 45th target gene is the hsa-miR-3135b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0415] The 46th target gene is the hsa-miR-4648 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0416] The 47th target gene is the hsa-miR-6816-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0417] The 48th target gene is the hsa-miR-4741 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0418] The 49th target gene is the hsa-miR-7150 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0419] The 50th target gene is the hsa-miR-6791-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0420] The 51st target gene is the hsa-miR-1247-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0421] The 52nd target gene is the hsa-miR-7977 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0422] The 53rd target gene is the hsa-miR-4497 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0423] The 54th target gene is the hsa-miR-6090 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0424] The 55th target gene is the hsa-miR-6781-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0425] The 56th target gene is the hsa-miR-6870-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0426] The 57th target gene is the hsa-miR-6729-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0427] The 58th target gene is the hsa-miR-4530 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0428] The 59th target gene is the hsa-miR-7847-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0429] The 60th target gene is the hsa-miR-6825-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0430] The 61st target gene is the hsa-miR-4674 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0431] The 62nd target gene is the hsa-miR-3917 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0432] The 63rd target gene is the hsa-miR-4707-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0433] The 64th target gene is the hsa-miR-6885-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0434] The 65th target gene is the hsa-miR-6722-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0435] The 66th target gene is the hsa-miR-4516 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0436] The 67th target gene is the hsa-miR-6757-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0437] The 68th target gene is the hsa-miR-6840-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0438] The 69th target gene is the hsa-miR-5195-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0439] The 70th target gene is the hsa-miR-6756-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0440] The 71st target gene is the hsa-miR-6800-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0441] The 72nd target gene is the hsa-miR-6727-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0442] The 73rd target gene is the hsa-miR-6126 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0443] The 74th target gene is the hsa-miR-6872-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0444] The 75th target gene is the hsa-miR-4446-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0445] The 76th target gene is the hsa-miR-1268a gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0446] The 77th target gene is the hsa-miR-1908-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0447] The 78th target gene is the hsa-miR-3679-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0448] The 79th target gene is the hsa-miR-4534 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0449] The 80th target gene is the hsa-miR-4675 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0450] The 81st target gene is the hsa-miR-7108-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0451] The 82nd target gene is the hsa-miR-6799-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0452] The 83rd target gene is the hsa-miR-4695-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0453] The 84th target gene is the hsa-miR-3178 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0454] The 85th target gene is the hsa-miR-5090 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0455] The 86th target gene is the hsa-miR-3180 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0456] The 87th target gene is the hsa-miR-1237-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0457] The 88th target gene is the hsa-miR-4758-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0458] The 89th target gene is the hsa-miR-3184-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0459] The 90th target gene is the hsa-miR-4286 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0460] The 91st target gene is the hsa-miR-6784-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0461] The 92nd target gene is the hsa-miR-6768-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0462] The 93rd target gene is the hsa-miR-6785-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0463] The 94th target gene is the hsa-miR-4706 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0464] The 95th target gene is the hsa-miR-711 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0465] The 96th target gene is the hsa-miR-1260a gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0466] The 97th target gene is the hsa-miR-6746-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0467] The 98th target gene is the hsa-miR-6089 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0468] The 99th target gene is the hsa-miR-6821-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0469] The 100th target gene is the hsa-miR-4667-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0470] The 101st target gene is the hsa-miR-8069 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0471] The 102nd target gene is the hsa-miR-4726-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0472] The 103rd target gene is the hsa-miR-6124 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0473] The 104th target gene is the hsa-miR-4532 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0474] The 105th target gene is the hsa-miR-4486 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0475] The 106th target gene is the hsa-miR-4728-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0476] The 107th target gene is the hsa-miR-4508 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0477] The 108th target gene is the hsa-miR-128-1-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0478] The 109th target gene is the hsa-miR-4513 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0479] The 110th target gene is the hsa-miR-6795-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0480] The 111th target gene is the hsa-miR-4689 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0481] The 112th target gene is the hsa-miR-6763-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0482] The 113th target gene is the hsa-miR-8072 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0483] The 114th target gene is the hsa-miR-6765-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0484] The 115th target gene is the hsa-miR-4419b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0485] The 116th target gene is the hsa-miR-7641 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0486] The 117th target gene is the hsa-miR-3928-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0487] The 118th target gene is the hsa-miR-1227-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0488] The 119th target gene is the hsa-miR-4492 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0489] The 120th target gene is the hsa-miR-296-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0490] The 121st target gene is the hsa-miR-6769a-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0491] The 122nd target gene is the hsa-miR-6889-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0492] The 123rd target gene is the hsa-miR-4632-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0493] The 124th target gene is the hsa-miR-4505 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0494] The 125th target gene is the hsa-miR-3154 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0495] The 126th target gene is the hsa-miR-3648 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0496] The 127th target gene is the hsa-miR-4442 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0497] The 128th target gene is the hsa-miR-3141 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0498] The 129th target gene is the hsa-miR-7113-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0499] The 130th target gene is the hsa-miR-6819-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0500] The 131st target gene is the hsa-miR-3195 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0501] The 132nd target gene is the hsa-miR-1199-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0502] The 133rd target gene is the hsa-miR-6738-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0503] The 134th target gene is the hsa-miR-4656 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0504] The 135th target gene is the hsa-miR-6820-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0505] The 136th target gene is the hsa-miR-615-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0506] The 137th target gene is the hsa-miR-486-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0507] The 138th target gene is the hsa-miR-1225-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0508] The 139th target gene is the hsa-miR-760 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0509] The 140th target gene is the hsa-miR-187-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0510] The 141st target gene is the hsa-miR-1203 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0511] The 142nd target gene is the hsa-miR-7110-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0512] The 143rd target gene is the hsa-miR-371a-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0513] The 144th target gene is the hsa-miR-939-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0514] The 145th target gene is the hsa-miR-575 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0515] The 146th target gene is the hsa-miR-92b-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 2).
[0516] The 147th target gene is the hsa-miR-887-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0517] The 148th target gene is the hsa-miR-920 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0518] The 149th target gene is the hsa-miR-1915-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0519] The 150th target gene is the hsa-miR-1231 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0520] The 151st target gene is the hsa-miR-663b gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0521] The 152nd target gene is the hsa-miR-1225-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0522] The 153rd target gene is the hsa-miR-4763-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0523] The 154th target gene is the hsa-miR-3656 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0524] The 155th target gene is the hsa-miR-4488 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0525] The 156th target gene is the hsa-miR-125a-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0526] The 157th target gene is the hsa-miR-1469 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0527] The 158th target gene is the hsa-miR-1228-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0528] The 159th target gene is the hsa-miR-6798-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0529] The 160th target gene is the hsa-miR-1268b gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0530] The 161st target gene is the hsa-miR-6732-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0531] The 162nd target gene is the hsa-miR-1915-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0532] The 163rd target gene is the hsa-miR-4433b-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0533] The 164th target gene is the hsa-miR-1207-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0534] The 165th target gene is the hsa-miR-4433-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0535] The 166th target gene is the hsa-miR-6879-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0536] The 167th target gene is the hsa-miR-4417 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0537] The 168th target gene is the hsa-miR-30c-1-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0538] The 169th target gene is the hsa-miR-4638-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0539] The 170th target gene is the hsa-miR-6088 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0540] The 171st target gene is the hsa-miR-4270 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0541] The 172nd target gene is the hsa-miR-6782-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0542] The 173rd target gene is the hsa-miR-665 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0543] The 174th target gene is the hsa-miR-486-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0544] The 175th target gene is the hsa-miR-4655-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0545] The 176th target gene is the hsa-miR-1275 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0546] The 177th target gene is the hsa-miR-6806-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0547] The 178th target gene is the hsa-miR-614 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0548] The 179th target gene is the hsa-miR-3937 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0549] The 180th target gene is the hsa-miR-6752-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0550] The 181st target gene is the hsa-miR-6771-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer.
[0551] The 182nd target gene is the hsa-miR-4450 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0552] The 183rd target gene is the hsa-miR-211-3p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0553] The 184th target gene is the hsa-miR-663a gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of this gene or its transcripts can serve as markers for prostate cancer (Patent Document 1).
[0554] The 185th target gene is the hsa-miR-6842-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0555] The 186th target gene is the hsa-miR-7114-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0556] The 187th target gene is the hsa-miR-6779-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for prostate cancer.
[0557] The 580th target gene is the hsa-miR-204-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0558] The 581st target gene is the hsa-miR-642a-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0559] The 582nd target gene is the hsa-miR-762 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0560] The 583rd target gene is the hsa-miR-1202 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0561] The 584th target gene is the hsa-miR-3162-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0562] The 585th target gene is the hsa-miR-3196 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0563] The 586th target gene is the hsa-miR-3622a-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0564] The 587th target gene is the hsa-miR-3665 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0565] The 588th target gene is the hsa-miR-3940-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0566] The 589th target gene is the hsa-miR-4294 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0567] The 590th target gene is the hsa-miR-4466 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0568] The 591st target gene is the hsa-miR-4476 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0569] The 592nd target gene is the hsa-miR-4723-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0570] The 593rd target gene is the hsa-miR-4725-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0571] The 594th target gene is the hsa-miR-4730 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0572] The 595th target gene is the hsa-miR-4739 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0573] The 596th target gene is the hsa-miR-4787-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0574] The 597th target gene is the hsa-miR-5787 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0575] The 598th target gene is the hsa-miR-6085 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0576] The 599th target gene is the hsa-miR-6717-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0577] The 600th target gene is the hsa-miR-6724-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0578] The 601st target gene is the hsa-miR-6777-5p gene, its homologs, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0579] The 602nd target gene is the hsa-miR-6778-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0580] The 603rd target gene is the hsa-miR-6787-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0581] The 604th target gene is the hsa-miR-6789-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0582] The 605th target gene is the hsa-miR-6845-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0583] The 606th target gene is the hsa-miR-6893-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for prostate cancer.
[0584] The 607th target gene is the hsa-miR-16-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for prostate cancer (Patent Document 2).
[0585] The 608th target gene is the hsa-miR-423-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for prostate cancer (Patent Document 2).
[0586] The 609th target gene is the hsa-miR-451a gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for prostate cancer (Patent Document 2).
[0587] The 610th target gene is the hsa-miR-564 gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for prostate cancer (Patent Document 2).
[0588] The 611th target gene is the hsa-miR-671-5p gene, its homologues, its transcription products, or its mutants or derivatives. There have been reports that changes in the expression of genes or their transcripts can serve as markers for prostate cancer (Patent Document 2).
[0589] 2. Nucleic acid probes or primers for prostate cancer detection
[0590] In the present invention, a nucleic acid capable of specifically binding to a target nucleic acid serving as the above-mentioned prostate cancer marker can be used as a nucleic acid for detecting or diagnosing prostate cancer, such as a nucleic acid probe or primer.
[0591] In the present invention, the nucleic acid probe or primer that can be used to detect prostate cancer or can be used to diagnose prostate cancer can qualitatively and / or quantitatively measure the presence, expression level or presence level of the target nucleic acid that is the above-mentioned prostate cancer marker, such as hsa-miR-4443, hsa-miR-1908-5p, hsa-miR-4257, hsa-miR-3197, hsa-miR-3188, hsa-miR-4649-5p, hsa-miR-1343-3p, hsa-miR-6861-5p, hsa-miR-1343-5p, hsa-miR-642b-3p, hsa-miR-6741-5 p, hsa-miR-4745-5p, hsa-miR-6826-5p, hsa-miR-3663-3p, hsa-miR-3131, hsa-miR-92a-2-5p, hsa-miR-4258, hsa-miR-4448, hsa-miR-6125, hsa-m iR-6880-5p, hsa-miR-6132, hsa-miR-4467, hsa-miR-6749-5p, hsa-miR-2392, hsa-miR-1273g-3p, hsa-miR-4746-3p, hsa-miR-1914-3p, hsa-miR-78 45-5p, hsa-miR-6726-5p, hsa-miR-128-2-5p, hsa-miR-4651, hsa-miR-6765-3p, hsa-miR-3185, hsa-miR-4792, hsa-miR-6887-5p, hsa-miR-5572, h sa-miR-3619-3p, hsa-miR-6780b-5p, hsa-miR-4707-5p, hsa-miR-8063, hsa-miR-4454, hsa-miR-4525, hsa-miR-7975, hsa-miR-744-5p, hsa-miR-31 35b, hsa-miR-4648, hsa-miR-6816-5p, hsa-miR-4741, hsa-miR-7150, hsa-miR-6791-5p, hsa-miR-1247-3p, hsa-miR-7977, hsa-miR-4497, hsa-miR -6090, hsa-miR-6781-5p, hsa-miR-6870-5p, hsa-miR-6729-5p, hsa-miR-4530, hsa-miR-7847-3p, hsa-miR-6825-5p, hsa-miR-4674, hsa-miR-3917,hsa-miR-4707-3p, hsa-miR-6885-5p, hsa-miR-6722-3p, hsa-miR-4516, hsa-miR-6757-5p, hsa-miR-6840-3p, hsa-miR-5195-3p, hsa-miR-6756-5 p、hsa-miR-6800-5p、hsa-miR-6727-5p、hsa-miR-6126、hsa-miR-6872-3p、hsa-miR-4446-3p、hsa-miR-1268a、hsa-miR-1908-3p、hsa-miR-3679-5p hsa-miR-4534, hsa-miR-4675, hsa-miR-7108-5p, hsa-miR-6799-5p, hsa-miR-4695-5p, hsa-miR-3178, hsa-miR-5090, hsa-miR-3180, hsa-miR-1 237-5p, hsa-miR-4758-5p, hsa-miR-3184-5p, hsa-miR-4286, hsa-miR-6784-5p, hsa-miR-6768-5p, hsa-miR-6785-5p, hsa-miR-4706, hsa-miR-711 hsa-miR-1260a, hsa-miR-6746-5p, hsa-miR-6089, hsa-miR-6821-5p, hsa-miR-4667-5p, hsa-miR-8069, hsa-miR-4726-5p, hsa-miR-6124, hsa-m iR-4532, hsa-miR-4486, hsa-miR-4728-5p, hsa-miR-4508, hsa-miR-128-1-5p, hsa-miR-4513, hsa-miR-6795-5p, hsa-miR-4689, hsa-miR-6763-5p hsa-miR-8072, hsa-miR-6765-5p, hsa-miR-4419b, hsa-miR-7641, hsa-miR-3928-3p, hsa-miR-1227-5p, hsa-miR-4492, hsa-miR-296-3p, hsa-mi R-6769a-5p、hsa-miR-6889-5p、hsa-miR-4632-5p、hsa-miR-4505、hsa-miR-3154、hsa-miR-3648、hsa-miR-4442、hsa-miR-3141、hsa-miR-7113-3p、hsa-miR-6819-5p, hsa-miR-3195, hsa-miR-1199-5p, hsa-miR-6738-5p, hsa-miR-4656, hsa-miR-6820-5p, hsa-miR-204-3p, hsa-miR-642a-3p, hsa-miR-7 62. hsa-miR-1202, hsa-miR-3162-5p, hsa-miR-3196, hsa-miR-3622a-5p, hsa-miR-3665, hsa-miR-3940-5p, hsa-miR-4294, hsa-miR-4466, hsa-miR-4476, h hsa-miR-4723-5p, hsa-miR-4725-3p, hsa-miR-4730, hsa-miR-4739, hsa-miR-4787-5p, hsa-miR-5787, hsa-miR-6085, hsa-miR-6717-5p, hsa-miR-6724-5p, hsa-miR-6777-5p, hsa-miR-6778-5p, hsa-miR-6787-5p, hsa-miR-6789-5p, hsa-miR-6845-5p, or hsa-miR-6893-5p, or a combination thereof, or a homologue thereof, a transcription product thereof, a mutant or a derivative thereof.
[0592] Regarding the above-mentioned target nucleic acids, the expression levels of these target nucleic acids in subjects suffering from prostate cancer may be increased or decreased (hereinafter referred to as "increase / decrease") depending on the type of the target nucleic acid. Therefore, the nucleic acids of the present invention can be used to measure the expression levels of the above-mentioned target nucleic acids in body fluids derived from subjects suspected of suffering from prostate cancer (e.g., humans) and body fluids derived from healthy subjects, and compare these, thereby effectively detecting prostate cancer.
[0593] The nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 135 and 580 to 606, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 135 and 580 to 606.
[0594] The nucleic acid probes or primers that can be used in the present invention may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of sequence numbers 136 to 152 and 607 to 611, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of sequence numbers 136 to 152 and 607 to 611.
[0595] The nucleic acid probe or primer that can be used in the present invention may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of at least one base sequence represented by sequence numbers 153 to 187, or a primer for amplifying a polynucleotide consisting of at least one base sequence represented by sequence numbers 153 to 187.
[0596] Specifically, the nucleic acid probe or primer comprises a polynucleotide group selected from a base sequence shown in any one of SEQ ID NOs: 1 to 684 or a base sequence in which u is t in the base sequence, and a complementary polynucleotide group thereof, a polynucleotide group and a complementary polynucleotide group that hybridize under stringent conditions (described later) with a DNA consisting of a base sequence complementary to the base sequence, and a polynucleotide group containing 15 or more, preferably 17 or more, consecutive bases in the base sequence of these polynucleotide groups. These polynucleotides can be used as nucleic acid probes and primers for detecting the prostate cancer marker as a target nucleic acid.
[0597] More specifically, examples of nucleic acid probes or primers that can be used in the present invention include any one or more polynucleotides selected from the following polynucleotides (a) to (e).
[0598] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0599] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606,
[0600] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0601] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, or a base sequence in which u is t in the base sequence, and
[0602] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0603] The nucleic acid probe or primer that can be used in the present invention may further contain a polynucleotide as shown in any one of the following (f) to (j), in addition to at least one polynucleotide selected from any one of the polynucleotides (a) to (e).
[0604] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in such a base sequence, a variant of such a polynucleotide, a derivative of such a polynucleotide, or a fragment of such a polynucleotide comprising 15 or more consecutive bases,
[0605] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 136 to 152, and 607 to 611,
[0606] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0607] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, or a base sequence in which u is t in the base sequence, and
[0608] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0609] The nucleic acid probe or primer that can be used in the present invention may contain, in addition to at least one polynucleotide selected from any one of the polynucleotides (a) to (j) above, a polynucleotide as shown in any one of the following (k) to (o).
[0610] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0611] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 153 to 187,
[0612] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0613] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, and
[0614] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0615] The "fragment thereof comprising 15 or more consecutive bases" in the above-mentioned polynucleotide means that in the base sequence of each polynucleotide, it may contain, for example, a consecutive number of bases ranging from 15 to less than the total number of bases in the sequence, from 17 to less than the total number of bases in the sequence, from 19 to less than the total number of bases in the sequence, etc., but is not limited thereto.
[0616] Any of the aforementioned polynucleotides or fragments thereof used in the present invention may be DNA or RNA.
[0617] The polynucleotides that can be used in the present invention can be produced using common techniques such as DNA recombination technology, PCR, and methods using a DNA / RNA automatic synthesizer.
[0618] For DNA recombination technology and PCR method, for example, the techniques described in Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989) and the like can be used.
[0619] Human-derived hsa-miR-4443, hsa-miR-1908-5p, hsa-miR-4257, hsa-miR-3197, hsa-miR-3188, hsa-miR-4649-5p, hsa-miR-1343-3p, hsa-miR-6861-5p, hsa-miR-1343-5p, hsa-miR-642b-3p, hsa-miR-6741-5p, hsa-miR-4745-5p, hsa-miR-6826-5p, hsa-miR-3663-3p, hsa-miR-3131, hsa-miR-92a-2-5p, hsa-miR-4258, hsa-miR-4448, hsa-miR-6125, hsa-miR-6880-5p, hsa-miR-6132, hsa-miR-4467, hsa-miR-6749-5p, hsa-miR-2392, hsa-miR-1273g-3p, hsa-miR-4746-3p, hsa-miR-1914-3p, hsa-miR-7845-5p, hsa-miR-6726-5p, hsa-miR-128-2-5p, hsa-miR-4651, hsa-miR-6765-3p, hsa-miR-3185, hsa-miR-4792, hsa-miR-6887-5p, hsa-miR-5572, hsa-miR-3619-3p, hsa-miR-6780b-5p, hsa-miR-4707-5p, hsa-miR-8063, hsa-miR-4454, hsa-miR-4525, hsa-miR-7975, hsa-miR-744-5p, hsa-miR-3135b, hsa-miR-4648, hsa-miR-6816-5p, hsa-miR-4741, hsa-miR-7150, hsa-miR-6791-5p, hsa-miR-1247-3p, hsa-miR-7977, hsa-miR-4497, hsa-miR-6090, hsa-miR-6781-5p, hsa-miR-6870-5p, hsa-miR-6729-5p, hsa-miR-4530, hsa-miR-7847-3p, hsa-miR-6825-5p, hsa-miR-4674, hsa-miR-3917, hsa-miR-4707-3p, hsa-miR-6885-5p, hsa-miR-6722-3p, hsa-miR-4516, as shown by serial numbers 1 to 187 and 580 to 611hsa-miR-6757-5p、hsa-miR-6840-3p、hsa-miR-5195-3p、hsa-miR-6756-5p、hsa-miR-6800-5p、hsa-miR-6727-5p、hsa-miR-6126、hsa-miR-6872-3p、 hsa-miR-4446-3p, hsa-miR-1268a, hsa-miR-1908-3p, hsa-miR-3679-5p, hsa-miR-4534, hsa-miR-4675, hsa-miR-7108-5p, hsa-miR-6799-5p, hsa-m iR-4695-5p, hsa-miR-3178, hsa-miR-5090, hsa-miR-3180, hsa-miR-1237-5p, hsa-miR-4758-5p, hsa-miR-3184-5p, hsa-miR-4286, hsa-miR-6784-5 p、hsa-miR-6768-5p、hsa-miR-6785-5p、hsa-miR-4706、hsa-miR-711、hsa-miR-1260a、hsa-miR-6746-5p、hsa-miR-6089、hsa-miR-6821-5p、hsa-miR -4667-5p、hsa-miR-8069、hsa-miR-4726-5p、hsa-miR-6124、hsa-miR-4532、hsa-miR-4486、hsa-miR-4728-5p、hsa-miR-4508、hsa-miR-128-1-5p、hs a-miR-4513, hsa-miR-6795-5p, hsa-miR-4689, hsa-miR-6763-5p, hsa-miR-8072, hsa-miR-6765-5p, hsa-miR-4419b, hsa-miR-7641, hsa-miR-3928- 3p、hsa-miR-1227-5p、hsa-miR-4492、hsa-miR-296-3p、hsa-miR-6769a-5p、hsa-miR-6889-5p、hsa-miR-4632-5p、hsa-miR-4505、hsa-miR-3154、hsa -miR-3648、hsa-miR-4442、hsa-miR-3141、hsa-miR-7113-3p、hsa-miR-6819-5p、hsa-miR-3195、hsa-miR-1199-5p、hsa-miR-6738-5p、hsa-miR-4656、hsa-miR-6820-5p, hsa-miR-204-3p, hsa-miR-642a-3p, hsa-miR-762, hsa-miR-1202, hsa-miR-3162-5p, hsa-miR-3196, hsa-miR-3622a-5p, hsa-miR -3665、hsa-miR-3940-5p、hsa-miR-4294、hsa-miR-4466、hsa-miR-4476、hsa-miR-4723-5p、hsa-miR-4725-3p、hsa-miR-4730、hsa-miR-4739、hsa-mi R-4787-5p、hsa-miR-5787、hsa-miR-6085、hsa-miR-6717-5p、hsa-miR-6724-5p、hsa-miR-6777-5p、hsa-miR-6778-5p、hsa-miR-6787-5p、hsa-miR-6 789-5p、hsa-miR-6845-5p、hsa-miR-6893-5p、hsa-miR-615-5p、hsa-miR-486-3p、hsa-miR-1225-3p、hsa-miR-760、hsa-miR-187-5p、hsa-miR-1203、 hsa-miR-7110-5p, hsa-miR-371a-5p, hsa-miR-939-5p, hsa-miR-575, hsa-miR-92b-5p, hsa-miR-887-3p, hsa-miR-920, hsa-miR-1915-5p, hsa-miR- 1231, hsa-miR-663b, hsa-miR-1225-5p, hsa-miR-16-5p, hsa-miR-423-5p, hsa-miR-451a, hsa-miR-564, hsa-miR-671-5p, hsa-miR-4763-3p, hsa-mi R-3656, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-1469, hsa-miR-1228-5p, hsa-miR-6798-5p, hsa-miR-1268b, hsa-miR-6732-5p, hsa-miR-1915-3 p、hsa-miR-4433b-3p、hsa-miR-1207-5p、hsa-miR-4433-3p、hsa-miR-6879-5p、hsa-miR-4417、hsa-miR-30c-1-3p、hsa-miR-4638-5p、hsa-miR-6088、Hsa-miR-4270, hsa-miR-6782-5p, hsa-miR-665, hsa-miR-486-5p, hsa-miR-4655-5p, hsa-miR-1275, hsa-miR-6806-5p, hsa-miR-614, hsa-miR-3937, hsa-miR-6752-5p, hsa-miR-6771-5p, hsa-miR-4450, hsa-miR-211-3p, hsa-miR-663a, hsa-miR-6842-5p, hsa-miR-7114-5p and hsa-miR-6779-5p are well known, and the methods for obtaining them are also known as described above. Therefore, by cloning this gene, a polynucleotide that can be used as a nucleic acid probe or primer in the present invention can be prepared.
[0620] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. This synthesis generally uses the phosphoramidite method, which allows the automatic synthesis of single-stranded DNA of up to about 100 bases. Automated DNA synthesizers are commercially available from companies such as Polygen, ABI, and Applied BioSystems.
[0621] Alternatively, the polynucleotide of the present invention can also be prepared by cDNA cloning. For example, the cDNA cloning technique can utilize the microRNA Cloning Kit (Wako).
[0622] Here, the sequences of nucleic acid probes and primers for detecting a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 187 and 580 to 611 do not exist in vivo as miRNA or its precursor. For example, the base sequences represented by SEQ ID NOs: 7 and 9 are generated from the precursor represented by SEQ ID NO: 194, but the precursor has Figure 1 In the hairpin-like structure shown, the base sequences shown in SEQ ID NO: 7 and SEQ ID NO: 9 have mismatches. Therefore, base sequences completely complementary to the base sequences shown in SEQ ID NO: 7 or SEQ ID NO: 9 do not naturally occur in vivo. Similarly, nucleic acid probes and primers used to detect the base sequences shown in any of SEQ ID NOs: 1 to 187 and 580 to 611 have artificial base sequences that do not exist in vivo.
[0623] 3. Prostate cancer detection kit or device
[0624] The present invention also provides a kit or device for detecting prostate cancer that contains one or more polynucleotides (which may contain mutants, fragments or derivatives; hereinafter sometimes referred to as detection polynucleotides) for measuring target nucleic acids that serve as prostate cancer markers and can be used as nucleic acid probes or primers in the present invention.
[0625] The target nucleic acid serving as a prostate cancer marker in the present invention is selected from the following Group 1.
[0626] miR-4443, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR- 4745-5p、miR-6826-5p、miR-3663-3p、miR-3131、miR-92a-2-5p、miR-4258、miR-4448、miR-6125、miR-6880-5p、miR-6132、miR-4467、miR-6749-5p、m iR-2392、miR-1273g-3p、miR-4746-3p、miR-1914-3p、miR-7845-5p、miR-6726-5p、miR-128-2-5p、miR-4651、miR-6765-3p、miR-3185、miR-4792、miR -6887-5p、miR-5572、miR-3619-3p、miR-6780b-5p、miR-4707-5p、miR-8063、miR-4454、miR-4525、miR-7975、miR-744-5p、miR-3135b、miR-4648、miR- 6816-5p、miR-4741、miR-7150、miR-6791-5p、miR-1247-3p、miR-7977、miR-4497、miR-6090、miR-6781-5p、miR-6870-5p、miR-6729-5p、miR-4530、mi R-7847-3p、miR-6825-5p、miR-4674、miR-3917、miR-4707-3p、miR-6885-5p、miR-6722-3p、miR-4516、miR-6757-5p、miR-6840-3p、miR-5195-3p、miR- 6756-5p、miR-6800-5p、miR-6727-5p、miR-6126、miR-6872-3p、miR-4446-3p、miR-1268a、miR-1908-3p、miR-3679-5p、miR-4534、miR-4675、miR-710 8-5p、miR-6799-5p、miR-4695-5p、miR-3178、miR-5090、miR-3180、miR-1237-5p、miR-4758-5p、miR-3184-5p、miR-4286、miR-6784-5p、miR-6768-5p、miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5 p、miR-4689、miR-6763-5p、miR-8072、miR-6765-5p、miR-4419b、miR-7641、miR-3928-3p、miR-1227-5p、miR-4492、miR-296-3p、miR-6769a-5p、miR-6889-5p、miR-4632-5p、miR-4505、miR-3154、miR-3648、miR-4442、miR-31 41、miR-7113-3p、miR-6819-5p、miR-3195、miR-1199-5p、miR-6738-5p、miR-4656、miR-6820-5p、miR-204-3p、miR-642a-3p、miR-762、miR-1202、miR-3162-5p、miR-3196、miR-3622a-5p、miR-3665、miR-3940-5p、miR-4294、m iR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p, and miR-6893-5p.
[0627] Depending on the situation, additional target nucleic acids that can be used for determination are selected from the following group 2: miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, miR-575, miR-92b-5p, miR-887-3p, miR-920, miR-1915-5p, miR-1231, miR-663b, miR-1225-5p, miR-16-5p, miR-423-5p, miR-451a, miR-564 and miR-671-5p.
[0628] Depending on the situation, additional target nucleic acids that can be used for the assay are selected from the following group 3: miR-4763-3p, miR-3656, miR-4488, miR-125a-3p, miR-1469, miR-1228-5p, miR-6798-5p, miR-1268b, miR-6732-5p, miR-1915-3p, miR-4433b-3p, miR-1207-5p, miR-4433-3p, miR-6879-5p, miR-4417, miR-30c-1 -3p,miR-4638-5p,miR-6088,miR-4270,miR-6782-5p,miR-665,miR-486-5p,miR-4655-5p,miR-1275,miR-6806-5p,miR- 614,miR-3937,miR-6752-5p,miR-6771-5p,miR-4450,miR-211-3p,miR-663a,miR-6842-5p,miR-7114-5p and miR-6779-5p.
[0629] The kit or device of the present invention contains a nucleic acid that can specifically bind to the above-mentioned target nucleic acid as a prostate cancer marker, preferably the nucleic acid probe or primer described in 2 above, specifically, one or more polynucleotides selected from the polynucleotide types described in 2 above or mutants of the polynucleotide, etc.
[0630] Specifically, the kit or device of the present invention may contain at least one or more of the following: a polynucleotide comprising a base sequence represented by any one of sequence numbers 1 to 135, 580 to 606, or a base sequence in which u is t in the base sequence (or consisting of a base sequence represented by any one of sequence numbers 1 to 135, 580 to 606, or a base sequence in which u is t in the base sequence), a polynucleotide comprising a complementary sequence thereof (or consisting of a complementary sequence thereof), a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising more than 15 consecutive bases.
[0631] The kit or device of the present invention may further include one or more of the following: a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 136 to 152, 607 to 611, or a base sequence in which u is t in such base sequence (or consisting of a base sequence represented by any one of SEQ ID NOs: 136 to 152, 607 to 611, or a base sequence in which u is t in such base sequence), a polynucleotide comprising (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to such polynucleotides under stringent conditions, or a mutant or fragment of such polynucleotide sequence comprising 15 or more consecutive bases.
[0632] The kit or device of the present invention may further include one or more of the following: a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 153 to 187 or a base sequence in which u is t in the base sequence (or consisting of a base sequence represented by any one of SEQ ID NOs: 153 to 187 or a base sequence in which u is t in the base sequence), a polynucleotide comprising a complementary sequence thereof (or consisting of a complementary sequence thereof), a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising 15 or more consecutive bases.
[0633] The fragments that can be contained in the kit or device of the present invention are, for example, one or more, preferably two or more, polynucleotides selected from the following (1) to (3).
[0634] (1) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 1 to 135 and 580 to 606, wherein u is t, or a complementary sequence thereof.
[0635] (2) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, or a complementary sequence thereof, in which u is t.
[0636] (3) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 153 to 187 in which u is t, or a complementary sequence thereof.
[0637] In a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 1 to 135, 580 to 606, or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0638] In addition, in a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 136 to 152, 607 to 611, or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0639] In addition, in a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 153 to 187, or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0640] In a preferred embodiment, the fragment may be a polynucleotide comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0641] In the present invention, the fragment size of a polynucleotide is, for example, a continuous number of bases ranging from 15 to less than the total number of bases in the base sequence of each polynucleotide, from 17 to less than the total number of bases in the sequence, from 19 to less than the total number of bases in the sequence, etc.
[0642] As a combination of the above-mentioned polynucleotides constituting the kit or device of the present invention, specifically, there can be mentioned cases where the above-mentioned polynucleotides composed of the base sequences represented by the sequence numbers shown in Table 1 (sequence numbers 1 to 187 and 580 to 611 corresponding to the miRNA markers in the table) are combined in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more. These are strictly illustrative, and all other possible combinations are included in the present invention.
[0643] For example, in the present invention, as the above-mentioned combination constituting a kit or device for distinguishing prostate cancer from a healthy body, it is desirable to combine two or more of the above-mentioned polynucleotides consisting of the base sequences represented by the sequence numbers shown in Table 1. Generally, a combination of two can obtain sufficient performance.
[0644] Specifically, as a combination of two polynucleotides composed of a base sequence or its complementary sequence for distinguishing prostate cancer from a healthy body, among the two combinations of the above-mentioned polynucleotides composed of the base sequences represented by sequence numbers 1 to 187 and 580 to 611, a combination containing at least one newly discovered polynucleotide composed of the base sequence represented by sequence numbers 1 to 135 is preferred.
[0645] In addition, as a combination of polynucleotides with cancer type specificity that can distinguish not only prostate cancer but also other cancers in healthy individuals, it is preferably selected from, for example, sequence numbers 1, 3, 4, 5, 6, 7, 9, 10, 12, 14, 15, 16, 17, 18, 20, 24, 29, 35, 37, 42, 51, 55, 58, 61, 63, 64, 67, 70, 72, 79, 82, 89, 91, 97, 98, 101, 103, 104, 112, 113, 114, 116, 119, 126, 135, 136, 139, 140, 141, 145, 147, 15 4, 155, 156, 158, 169, 173, 175, 178, 182, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610 and 611 of the group consisting of polynucleotides (hereinafter referred to as "cancer type specific polynucleotide group 1"), and multiple combinations of polynucleotides of other sequence numbers.
[0646] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish not only prostate cancer but also other cancers in healthy individuals, a combination of multiple polynucleotides selected from the cancer type-specific polynucleotide group 1 is more preferred.
[0647] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish not only prostate cancer in healthy subjects but also other cancers, among the combinations of multiple polynucleotides selected from the cancer type-specific polynucleotide group 1, a more preferred combination is a group consisting of at least one polynucleotide with sequence numbers 1, 12, 16, 37, 42, 63, 119, 126, 139, 173, 178, 599, 609 and 611 selected from the cancer type-specific polynucleotide group 1 (hereinafter referred to as "cancer type-specific polynucleotide group 2").
[0648] The number of combinations of the above-mentioned cancer type-specific polynucleotides can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more than 10 combinations, more preferably 4 or more combinations, and usually 4 combinations can obtain sufficient performance.
[0649] The following non-limiting examples include combinations of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 1 or its complementary sequence, and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0650] (1) Combination of SEQ ID NOs: 1, 63, 139, and 600 (markers: hsa-miR-4443, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-6724-5p)
[0651] (2) Combination of SEQ ID NOs: 1, 12, 63, and 599 (markers: hsa-miR-4443, hsa-miR-4745-5p, hsa-miR-4707-3p, and hsa-miR-6717-5p)
[0652] (3) Combination of SEQ ID NOs: 1, 141, 173, and 599 (markers: hsa-miR-4443, hsa-miR-1203, hsa-miR-665, and hsa-miR-6717-5p)
[0653] (4) Combination of SEQ ID NOs: 1, 16, 139, and 178 (markers: hsa-miR-4443, hsa-miR-92a-2-5p, hsa-miR-760, and hsa-miR-614)
[0654] (5) Combination of SEQ ID NOs: 1, 63, 173, and 599 (markers: hsa-miR-4443, hsa-miR-4707-3p, hsa-miR-665, and hsa-miR-6717-5p)
[0655] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 12 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0656] (1) Combination of SEQ ID NOs: 12, 42, 63, and 609 (markers: hsa-miR-4745-5p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-451a)
[0657] (2) Combination of SEQ ID NOs: 12, 16, 135, and 156 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-6820-5p, and hsa-miR-125a-3p)
[0658] (3) Combination of SEQ ID NOs: 12, 16, 169, and 178 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-4638-5p, and hsa-miR-614)
[0659] (4) Combination of SEQ ID NOs: 12, 16, 139, and 601 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-760, and hsa-miR-6777-5p)
[0660] (5) Combination of SEQ ID NOs: 12, 16, 42, and 607 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-4525, and hsa-miR-16-5p)
[0661] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 16 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0662] (1) Combination of SEQ ID NOs: 16, 18, 139, and 178 (markers: hsa-miR-92a-2-5p, hsa-miR-4448, hsa-miR-760, and hsa-miR-614)
[0663] (2) Combination of SEQ ID NOs: 12, 16, 37, and 178 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-614)
[0664] (3) Combination of SEQ ID NOs: 12, 16, 37, and 599 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-6717-5p)
[0665] (4) Combination of SEQ ID NOs: 12, 16, 37, and 97 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-6746-5p)
[0666] (5) Combination of SEQ ID NOs: 12, 14, 16, and 599 (markers: hsa-miR-4745-5p, hsa-miR-3663-3p, hsa-miR-92a-2-5p, and hsa-miR-6717-5p)
[0667] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 37 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0668] (1) Combination of SEQ ID NOs: 37, 63, 139, and 611 (markers: hsa-miR-3619-3p, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-671-5p)
[0669] (2) Combination of SEQ ID NOs: 37, 42, 63, and 178 (markers: hsa-miR-3619-3p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-614)
[0670] (3) Combination of SEQ ID NOs: 37, 42, 63, and 599 (markers: hsa-miR-3619-3p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-6717-5p)
[0671] (4) Combination of SEQ ID NOs: 37, 42, 63, and 139 (markers: hsa-miR-3619-3p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-760)
[0672] (5) Combination of SEQ ID NOs: 12, 16, 37, and 603 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-6787-5p)
[0673] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 42 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0674] (1) Combination of SEQ ID NOs: 42, 63, 607, and 611 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-16-5p, and hsa-miR-671-5p)
[0675] (2) Combination of SEQ ID NOs: 42, 63, 609, and 611 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-451a, and hsa-miR-671-5p)
[0676] (3) Combination of SEQ ID NOs: 42, 63, 173, and 599 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-665, and hsa-miR-6717-5p)
[0677] (4) Combination of SEQ ID NOs: 12, 16, 42, and 609 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-4525, and hsa-miR-451a)
[0678] (5) Combination of SEQ ID NOs: 42, 63, 91, and 609 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-6784-5p, and hsa-miR-451a)
[0679] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 63 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0680] (1) Combination of SEQ ID NOs: 10, 42, 63, and 599 (markers: hsa-miR-642b-3p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-6717-5p)
[0681] (2) Combination of SEQ ID NOs: 42, 63, 599, and 609 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-6717-5p, and hsa-miR-451a)
[0682] (3) Combination of SEQ ID NOs: 42, 63, 583, and 609 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-1202, and hsa-miR-451a)
[0683] (4) Combination of SEQ ID NOs: 37, 42, 63, and 611 (markers: hsa-miR-3619-3p, hsa-miR-4525, hsa-miR-4707-3p, and hsa-miR-671-5p)
[0684] (5) Combination of SEQ ID NOs: 12, 63, 70, and 599 (markers: hsa-miR-4745-5p, hsa-miR-4707-3p, hsa-miR-6756-5p, and hsa-miR-6717-5p)
[0685] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 119 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0686] (1) Combination of SEQ ID NOs: 12, 16, 37, and 119 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-4492)
[0687] (2) Combination of SEQ ID NOs: 37, 63, 119, and 584 (markers: hsa-miR-3619-3p, hsa-miR-4707-3p, hsa-miR-4492, and hsa-miR-3162-5p)
[0688] (3) Combination of SEQ ID NOs: 63, 119, 173, and 178 (markers: hsa-miR-4707-3p, hsa-miR-4492, hsa-miR-665, and hsa-miR-614)
[0689] (4) Combination of SEQ ID NOs: 63, 119, 158, and 173 (markers: hsa-miR-4707-3p, hsa-miR-4492, hsa-miR-1228-5p, and hsa-miR-665)
[0690] (5) Combination of SEQ ID NOs: 63, 119, 173, and 605 (markers: hsa-miR-4707-3p, hsa-miR-4492, hsa-miR-665, and hsa-miR-6845-5p)
[0691] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 126 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0692] (1) Combination of SEQ ID NOs: 16, 126, 597, and 599 (markers: hsa-miR-92a-2-5p, hsa-miR-3648, hsa-miR-5787, and hsa-miR-6717-5p)
[0693] (2) Combination of SEQ ID NOs: 16, 42, 126, and 599 (markers: hsa-miR-92a-2-5p, hsa-miR-4525, hsa-miR-3648, and hsa-miR-6717-5p)
[0694] (3) Combination of SEQ ID NOs: 16, 126, 139, and 601 (markers: hsa-miR-92a-2-5p, hsa-miR-3648, hsa-miR-760, and hsa-miR-6777-5p)
[0695] (4) Combination of SEQ ID NOs: 16, 126, 593, and 599 (markers: hsa-miR-92a-2-5p, hsa-miR-3648, hsa-miR-4725-3p, and hsa-miR-6717-5p)
[0696] (5) Combination of SEQ ID NOs: 15, 16, 126, and 599 (markers: hsa-miR-3131, hsa-miR-92a-2-5p, hsa-miR-3648, and hsa-miR-6717-5p)
[0697] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 139 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0698] (1) Combination of SEQ ID NOs: 37, 63, 139, and 584 (markers: hsa-miR-3619-3p, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-3162-5p)
[0699] (2) Combination of SEQ ID NOs: 63, 139, 173, and 178 (markers: hsa-miR-4707-3p, hsa-miR-760, hsa-miR-665, and hsa-miR-614)
[0700] (3) Combination of SEQ ID NOs: 16, 63, 139, and 601 (markers: hsa-miR-92a-2-5p, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-6777-5p)
[0701] (4) Combination of SEQ ID NOs: 37, 63, 139, and 600 (markers: hsa-miR-3619-3p, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-6724-5p)
[0702] (5) Combination of SEQ ID NOs: 16, 139, 178, and 586 (markers: hsa-miR-92a-2-5p, hsa-miR-760, hsa-miR-614, and hsa-miR-3622a-5p)
[0703] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 173 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0704] (1) Combination of SEQ ID NOs: 63, 139, 173, and 599 (markers: hsa-miR-4707-3p, hsa-miR-760, hsa-miR-665, and hsa-miR-6717-5p)
[0705] (2) Combination of SEQ ID NOs: 63, 119, 173, and 581 (markers: hsa-miR-4707-3p, hsa-miR-4492, hsa-miR-665, and hsa-miR-642a-3p)
[0706] (3) Combination of SEQ ID NOs: 63, 173, 582, and 599 (markers: hsa-miR-4707-3p, hsa-miR-665, hsa-miR-762, and hsa-miR-6717-5p)
[0707] (4) Combination of SEQ ID NOs: 63, 136, 173, and 599 (markers: hsa-miR-4707-3p, hsa-miR-615-5p, hsa-miR-665, and hsa-miR-6717-5p)
[0708] (5) Combination of SEQ ID NOs: 29, 63, 173, and 178 (markers: hsa-miR-6726-5p, hsa-miR-4707-3p, hsa-miR-665, and hsa-miR-614)
[0709] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 178 or its complementary sequence, and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0710] (1) Combination of SEQ ID NOs: 16, 139, 178, and 601 (markers: hsa-miR-92a-2-5p, hsa-miR-760, hsa-miR-614, and hsa-miR-6777-5p)
[0711] (2) Combination of SEQ ID NOs: 16, 37, 139, and 178 (markers: hsa-miR-92a-2-5p, hsa-miR-3619-3p, hsa-miR-760, and hsa-miR-614)
[0712] (3) Combination of SEQ ID NOs: 1, 12, 16, and 178 (markers: hsa-miR-4443, hsa-miR-4745-5p, hsa-miR-92a-2-5p, and hsa-miR-614)
[0713] (4) Combination of SEQ ID NOs: 1, 63, 173, and 178 (markers: hsa-miR-4443, hsa-miR-4707-3p, hsa-miR-665, and hsa-miR-614)
[0714] (5) Combination of SEQ ID NOs: 16, 139, 178, and 597 (markers: hsa-miR-92a-2-5p, hsa-miR-760, hsa-miR-614, and hsa-miR-5787)
[0715] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 599 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0716] (1) Combination of SEQ ID NOs: 12, 37, 63, and 599 (markers: hsa-miR-4745-5p, hsa-miR-3619-3p, hsa-miR-4707-3p, and hsa-miR-6717-5p)
[0717] (2) Combination of SEQ ID NOs: 42, 58, 63, and 599 (markers: hsa-miR-4525, hsa-miR-4530, hsa-miR-4707-3p, and hsa-miR-6717-5p)
[0718] (3) Combination of SEQ ID NOs: 1, 12, 16, and 599 (markers: hsa-miR-4443, hsa-miR-4745-5p, hsa-miR-92a-2-5p, and hsa-miR-6717-5p)
[0719] (4) Combination of SEQ ID NOs: 63, 119, 173, and 599 (markers: hsa-miR-4707-3p, hsa-miR-4492, hsa-miR-665, and hsa-miR-6717-5p)
[0720] (5) Combination of SEQ ID NOs: 16, 18, 139, and 599 (markers: hsa-miR-92a-2-5p, hsa-miR-4448, hsa-miR-760, and hsa-miR-6717-5p)
[0721] Furthermore, non-limiting examples include combinations of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 609 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0722] (1) Combination of SEQ ID NOs: 42, 63, 585, and 609 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-3196, and hsa-miR-451a)
[0723] (2) Combination of SEQ ID NOs: 42, 63, 592, and 609 (markers: hsa-miR-4525, hsa-miR-4707-3p, hsa-miR-4723-5p, and hsa-miR-451a)
[0724] (3) Combination of SEQ ID NOs: 18, 42, 581, and 609 (markers: hsa-miR-4448, hsa-miR-4525, hsa-miR-642a-3p, and hsa-miR-451a)
[0725] (4) Combination of SEQ ID NOs: 12, 16, 599, and 609 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-6717-5p, and hsa-miR-451a)
[0726] (5) Combination of SEQ ID NOs: 16, 126, 599, and 609 (markers: hsa-miR-92a-2-5p, hsa-miR-3648, hsa-miR-6717-5p, and hsa-miR-451a)
[0727] Furthermore, non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 611 or its complementary sequence and a polynucleotide consisting of the base sequences represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1 or their complementary sequences.
[0728] (1) Combination of SEQ ID NOs: 12, 16, 37, and 611 (markers: hsa-miR-4745-5p, hsa-miR-92a-2-5p, hsa-miR-3619-3p, and hsa-miR-671-5p)
[0729] (2) Combination of SEQ ID NOs: 1, 63, 139, and 611 (markers: hsa-miR-4443, hsa-miR-4707-3p, hsa-miR-760, and hsa-miR-671-5p)
[0730] (3) Combination of SEQ ID NOs: 63, 158, 173, and 611 (markers: hsa-miR-4707-3p, hsa-miR-1228-5p, hsa-miR-665, and hsa-miR-671-5p)
[0731] (4) Combination of SEQ ID NOs: 16, 37, 139, and 611 (markers: hsa-miR-92a-2-5p, hsa-miR-3619-3p, hsa-miR-760, and hsa-miR-671-5p)
[0732] (5) Combination of SEQ ID NOs: 16, 37, 595, and 611 (markers: hsa-miR-92a-2-5p, hsa-miR-3619-3p, hsa-miR-4739, and hsa-miR-671-5p)
[0733] The kit or device of the present invention may contain, in addition to the polynucleotides of the present invention described above (which may include mutants, fragments, or derivatives), known polynucleotides capable of detecting prostate cancer or polynucleotides to be discovered in the future.
[0734] The kit of the present invention may contain, in addition to the polynucleotide of the present invention described above, and mutants or fragments thereof, an antibody for measuring a known prostate cancer detection marker such as PSA.
[0735] The polynucleotides and mutants or fragments thereof contained in the kit of the present invention may be packaged in different containers individually or in any combination.
[0736] The kit of the present invention may further include a kit for extracting nucleic acid (eg, total RNA) from body fluids, cells, or tissues, a fluorescent substance for labeling, an enzyme and culture medium for nucleic acid amplification, instructions for use, and the like.
[0737] The device of the present invention is a device for measuring cancer markers, wherein the nucleic acids such as the polynucleotides, mutants, derivatives, or fragments thereof described above in the present invention are, for example, measured to measure cancer markers bound to or attached to a solid phase. Examples of materials for the solid phase are plastic, paper, glass, silicon, etc., and from the perspective of ease of processing, the preferred material for the solid phase is plastic. The shape of the solid phase is arbitrary, for example, square, circular, long strip, membrane-shaped, etc. The device of the present invention includes, for example, a device for measuring by hybridization technology, specifically, blotting devices, nucleic acid arrays (such as microarrays, DNA chips, RNA chips, etc.), etc.
[0738] Nucleic acid array technology is a technology that uses the following methods to produce an array such as a chip by binding or attaching the above-mentioned nucleic acids one by one, and uses this array to measure target nucleic acids through hybridization. The methods include: methods of spotting nucleic acids on the surface of a solid phase that has been subjected to surface treatments such as L-lysine coating and / or introduction of functional groups such as amino groups and carboxyl groups as needed, using a high-density dispenser called a spotter or arrayer; methods of spraying nucleic acids onto a solid phase using an inkjet that ejects tiny droplets from a nozzle using a piezoelectric element; methods of sequentially synthesizing nucleotides on the solid phase, etc.
[0739] The kit or device of the present invention comprises a nucleic acid capable of specifically binding to at least one, preferably at least two, more preferably at least three, and most preferably at least five to all polynucleotides of the miRNA as a prostate cancer marker of the above-mentioned group 1. The kit or device of the present invention may further comprise a nucleic acid capable of specifically binding to at least one, preferably at least two, more preferably at least three, and most preferably at least five to all polynucleotides of the miRNA as a prostate cancer marker of the above-mentioned group 2, depending on the circumstances. The kit or device of the present invention may further comprise a nucleic acid capable of specifically binding to at least one, preferably at least two, more preferably at least three, and most preferably at least five to all polynucleotides of the miRNA as a prostate cancer marker of the above-mentioned group 3, depending on the circumstances.
[0740] The kit or device of the present invention can be used for the following 4 detections of prostate cancer.
[0741] 4. Prostate cancer detection methods
[0742] The present invention further provides a method for detecting prostate cancer, comprising: using the kit or device of the present invention described in 3 above (including the above-mentioned nucleic acid that can be used in the present invention), in vitro measuring miR-4443, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4443-5p, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p p,miR-4258,miR-4448,miR-6125,miR-6880-5p,miR-6132,miR-4467,miR-6749-5p,miR-2392,miR-1273g-3p,miR-4746-3p,miR-1914-3p,miR-7845 -5p,miR-6726-5p,miR-128-2-5p,miR-4651,miR-6765-3p,miR-3185,miR-4792,miR-6887-5p,miR-5572,miR-3619-3p,miR-6780b-5p,miR-4707-5p ,miR-8063,miR-4454,miR-4525,miR-7975,miR-744-5p,miR-3135b,miR-4648,miR-6816-5p,miR-4741,miR-7150,miR-6791-5p,miR-1247-3p,miR- 7977,miR-4497,miR-6090,miR-6781-5p,miR-6870-5p,miR-6729-5p,miR-4530,miR-7847-3p,miR-6825-5p,miR-4674,miR-3917,miR-4707-3p,miR -6885-5p,miR-6722-3p,miR-4516,miR-6757-5p,miR-6840-3p,miR-5195-3p,miR-6756-5p,miR-6800-5p,miR-6727-5p,miR-6126,miR-6872-3p,mi R-4446-3p,miR-1268a,miR-1908-3p,miR-3679-5p,miR-4534,miR-4675,miR-7108-5p,miR-6799-5p,miR-4695-5p,miR-3178,miR-5090,miR-3180,The expression levels of genes derived from prostate cancer as shown by miR-1237-5p, miR-4758-5p, miR-3184-5p, miR-4286, miR-6784-5p, miR-6768-5p, miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5p, miR-4689, miR-6763-5p, miR-8072, miR-6765-5p, miR-4419b, miR-7641, miR-3928-3p, miR-1227-5p, miR-4492, miR-296-3p, miR-6769a-5p, miR-6889-5p, miR-4632-5p, miR-4505, miR-3154, miR-3648, miR-4442, miR-3141, miR-7113-3p, miR-6819-5p, miR-3195, miR-1199-5p, miR-6738-5p, miR-4656, miR-6820-5p, miR-204-3p, miR-642a-3p, miR-762, miR-1202, miR-3162-5p, miR-3196, miR-3622a-5p, miR-3665, miR-3940-5p, miR-4294, miR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p and miR-6893-5p, and miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, miR-575, miR-92b-5p, miR-887-3p, miR-920, miR-1915-5p, miR-1231 selected from the following group as appropriate,The expression levels of prostate cancer-derived genes represented by miR-663b, miR-1225-5p, miR-16-5p, miR-423-5p, miR-451a, miR-564, and miR-671-5p, and miR-4763-3p, miR-3656, miR-4488, miR-125a-3p, miR-1469, miR-1228-5p selected from the following groups as appropriate ,miR-6798-5p,miR-1268b,miR-6732-5p,miR-1915-3p,miR-4433b-3p,miR-1207-5p,miR-4433 -3p,miR-6879-5p,miR-4417,miR-30c-1-3p,miR-4638-5p,miR-6088,miR-4270,miR-6782-5p,m iR-665,miR-486-5p,miR-4655-5p,miR-1275,miR-6806-5p,miR-614,miR-3937,miR-6752-5p, The former shown by miR-6771-5p, miR-4450, miR-211-3p, miR-663a, miR-6842-5p, miR-7114-5p and miR-6779-5p The expression level of a gene derived from prostate cancer, the expression level of one or more of the genes derived from prostate cancer shown in the above, and further the expression level of the above genes in the specimens and the control expression level of the healthy subjects (including non-prostate cancer patients) collected from the subjects suspected of having prostate cancer are compared, for example, when the expression level of the target nucleic acid in the specimen is statistically significantly different, the subject is evaluated as having prostate cancer.
[0743] The method of the present invention enables low-invasive early diagnosis of cancer with high sensitivity and specificity, thereby leading to early treatment and improved prognosis, and further enables monitoring of disease progression and the effectiveness of surgical treatment, radiotherapy, and chemotherapy.
[0744] As a method of extracting prostate cancer-derived genes from specimens such as blood, serum, and plasma of the present invention, it is particularly preferred to add and prepare the RNA extraction reagent in the 3D-Gene (registered trademark) RNA extraction reagent from liquid sample kit (Toray Industries, Inc.), but the general acid phenol method (acid guanidinium-phenol-chloroform (AGPC) method) can also be used, Trizol (registered trademark) (Life Technologies Co., Ltd.) can also be used, and RNA extraction reagents containing acid phenol such as Trizol (life technologies company) and Isogen (Nippon Gene Co., Ltd.) can also be added and prepared. Further, kits such as miRNeasy (registered trademark) Mini Kit (Qiagen Co., Ltd.) can be used, but are not limited to these methods.
[0745] The present invention further provides use of the kit or device of the present invention for in vitro detection of expression products of prostate cancer-derived miRNA genes in a subject-derived specimen.
[0746] In the above method of the present invention, the above kit or device contains the polynucleotides that can be used in the present invention, as described above, either singly or in all possible combinations.
[0747] In the detection or (gene) diagnosis of prostate cancer of the present invention, the polynucleotides contained in the kit or device of the present invention can be used as probes or primers. When used as primers, the polynucleotides can be used, for example, Life Technologies' TaqMan (registered trademark) MicroRNA Assays, Qiagen's miScript PCR System, etc., but are not limited to these methods.
[0748] The polynucleotides contained in the kits or devices of the present invention can be used as primers or probes in conventional methods for specifically detecting specific genes, such as hybridization techniques such as Northern blotting, Southern blotting, in situ hybridization, Northern hybridization, and Southern hybridization, and quantitative amplification techniques such as quantitative RT-PCR. As the test specimen, body fluids such as blood, serum, plasma, and urine are collected from the subject, depending on the type of detection method used. Alternatively, total RNA prepared from such body fluids using the above-described methods can be used, and further, various polynucleotides including cDNA prepared based on this RNA can be used.
[0749] The kit or device of the present invention is useful for diagnosing prostate cancer or detecting the presence or absence of prostate cancer. Specifically, detection of prostate cancer using the kit or device can be performed as follows: using a specimen such as blood, serum, plasma, or urine from a subject suspected of having prostate cancer, the expression level of a gene detected by a nucleic acid probe or primer contained in the kit or device is detected in vitro. When the expression level of the target miRNA marker measured by a polynucleotide (including mutants, fragments or derivatives thereof) composed of the base sequences represented by at least one of sequence numbers 1 to 135 and 580 to 606 or their complementary sequences, and the base sequences represented by one or more of sequence numbers 136 to 152, 607 to 611 or their complementary sequences, and the base sequences represented by one or more of sequence numbers 153 to 187 or their complementary sequences in the blood, serum, plasma, urine or other specimens of a subject suspected of having prostate cancer is statistically significantly different from their expression levels in the blood, serum, plasma, urine or other specimens of a healthy person, the subject can be evaluated as having prostate cancer.
[0750] The method of the present invention can be combined with imaging diagnostic methods such as rectal examination, transrectal prostate ultrasound examination, CT examination, MRI examination, bone scintigraphy, etc. The method of the present invention can specifically detect prostate cancer and can substantially distinguish it from other cancers.
[0751] The method for detecting whether a test sample using the kit or device of the present invention contains no expression products of genes derived from prostate cancer, or contains expression products of genes derived from prostate cancer, comprises: collecting body fluids such as blood, serum, plasma, and urine from the test sample, and measuring the expression level of the target gene contained therein using a single or multiple polynucleotides (including mutants, fragments, or derivatives) selected from the polynucleotide group of the present invention, thereby evaluating the presence or absence of prostate cancer or detecting prostate cancer. In addition, the method for detecting prostate cancer of the present invention can also be used to evaluate or diagnose, for example, the presence or absence of improvement in the disease or the degree of improvement when a therapeutic drug for improving the disease is administered to a prostate cancer patient.
[0752] The method of the present invention may include, for example, the following steps (a), (b) and (c):
[0753] (a) a step of contacting a sample derived from a subject with a polynucleotide in the kit or device of the present invention in vitro,
[0754] (b) a step of measuring the expression level of a target nucleic acid in a sample using the polynucleotide as a nucleic acid probe or primer,
[0755] (c) A step of evaluating the presence or absence of prostate cancer (cells) in the subject based on the result of (b).
[0756] Specifically, the present invention provides a method for detecting prostate cancer, which includes: using a substance capable of binding to a selected from miR-4443, miR-1908-5p, miR-4257, miR-3197, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4258, miR-4448, miR-6125, miR-6880-5p, miR-6132, miR-4467, miR-6749-5p, miR-2392, miR-1273g-3p, miR-4746-3p, miR-1914-3p, miR-7845-5p, miR-6726-5p, miR-128-2-5p, miR-4651, miR-6765-3p, miR-3185, miR-4792, miR-6887-5p, miR-5572, miR-3619-3p, miR-6780b-5p, miR-4707-5p, miR-8063, miR-4454, miR-4525, miR-7975, miR-744-5p, miR-3135b, miR-4648, miR-6816-5p, miR-4741, miR-7150, miR-6791-5p, miR-1247-3p, miR-7977, miR-4497, miR-6090, miR-6781-5p, miR-6870-5p, miR-6729-5p, miR-4530, miR-7847-3p, miR-6825-5p, miR-4674, miR-3917, miR-4707-3p, miR-6885-5p, miR-6722-3p, miR-4516, miR-6757-5p, miR-6840-3p, miR-5195-3p, miR-6756-5p, miR-6800-5p, miR-6727-5p, miR-6126, miR-6872-3p, miR-4446-3p, miR-1268a, miR-1908-3p, miR-3679-5p, miR-4534, miR-4675, miR-7108-5p, miR-6799-5p, miR-4695-5p, miR-3178, miR-5090, miR-3180, miR-1237-5p, miR-4758-5p, miR-3184-5pmiR-4286,miR-6784-5p,miR-6768-5p,miR-6785-5p,miR-4706,miR-711,miR-1260a,miR-6746-5p,miR-6089,miR-6821-5p,miR- 4667-5p,miR-8069,miR-4726-5p,miR-6124,miR-4532,miR-4486,miR-4728-5p,miR-4508,miR-128-1-5p,miR-4513,miR-6795-5 p,miR-4689,miR-6763-5p,miR-8072,miR-6765-5p,miR-4419b,miR-7641,miR-3928-3p,miR-1227-5p,miR-4492,miR-296-3p,mi R-6769a-5p,miR-6889-5p,miR-4632-5p,miR-4505,miR-3154,miR-3648,miR-4442,miR-3141,miR-7113-3p,miR-6819-5p,miR-31 95.miR-1199-5p,miR-6738-5p,miR-4656,miR-6820-5p,miR-204-3p,miR-642a-3p,miR-762,miR-1202,miR-3162-5p,miR-3196, miR-3622a-5p,miR-3665,miR-3940-5p,miR-4294,miR-4466,miR-4476,miR-4723-5p,miR-4725-3p,miR-4730,miR-4739,mi...
Claims
1. Use of a nucleic acid that can specifically bind to a prostate cancer marker for the manufacture of a kit for detecting prostate cancer, wherein the prostate cancer marker is selected from miR-3197, miR-1908-5p, miR-4257, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4258, miR-6125, miR-6880-5p p,miR-6132,miR-4467,miR-6749-5p,miR-2392,miR-1273g-3p,miR-4746-3p,miR-1914-3p,miR-7845-5p,miR-6726-5p,miR-128-2-5p,miR-4651, miR-6765-3p,miR-3185,miR-4792,miR-6887-5p,miR-5572,miR-3619-3p,miR-6780b-5p,miR-4707-5p,miR-8063,miR-4454,miR-4525,miR-7975,m iR-744-5p,miR-3135b,miR-4648,miR-6816-5p,miR-4741,miR-7150,miR-6791-5p,miR-1247-3p,miR-7977,miR-4497,miR-6090,miR-6781-5p,mi R-6870-5p,miR-6729-5p,miR-4530,miR-7847-3p,miR-6825-5p,miR-4674,miR-3917,miR-4707-3p,miR-6885-5p,miR-6722-3p,miR-4516,miR-675 7-5p,miR-6840-3p,miR-5195-3p,miR-6756-5p,miR-6800-5p,miR-6727-5p,miR-6126,miR-6872-3p,miR-4446-3p,miR-1268a,miR-1908-3p,miR- 3679-5p,miR-4534,miR-4675,miR-7108-5p,miR-6799-5p,miR-4695-5p,miR-3178,miR-5090,miR-3180,miR-1237-5p,miR-4758-5p,miR-3184-5p,At least one polynucleotide among miR-4286, miR-6784-5p, miR-6768-5p, miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5p, miR-4689, miR-6763-5p, miR-8072, miR-6765-5p, miR-4419b, miR-7641, miR-3928-3p, miR-1227-5p, miR-4492, miR-296-3p, miR-6769a-5p, miR-6889-5p, miR-4632-5p, miR-4505, miR-3154, miR-3648, miR-4442, miR-3141, miR-7113-3p, miR-6819-5p, miR-3195, miR-1199-5p, miR-6738-5p, miR-4656, miR-6820-5p, miR-204-3p, miR-642a-3p, miR-762, miR-1202, miR-3162-5p, miR-3196, miR-3622a-5p, miR-3665, miR-3940-5p, miR-4294, miR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p, and miR-6893-5p.
2. The use according to claim 1, wherein miR-3197 is hsa-miR-3197, miR-1908-5p is hsa-miR-1908-5p, miR-4257 is hsa-miR-4257, miR-3188 is hsa-miR-3188, miR-4649-5p is hsa-miR-4649-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6861-5p is hsa-miR-6861-5p, miR-1343-5p is hsa-miR-1343-5p, and miR-642b-3p is hsa-miR-644b-3p. 2b-3p, miR-6741-5p is hsa-miR-6741-5p, miR-4745-5p is hsa-miR-4745-5p, miR-6826-5p is hsa-miR-6826-5p, miR-3663-3p is hsa-miR-3663-3p, miR-3131 is hsa-miR-3131, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4258 is hsa-miR-4258, miR-6125 is hsa-miR-6125, miR-6880-5p is hsa-miR-6880-5p, miR- 6132 is hsa-miR-6132, miR-4467 is hsa-miR-4467, miR-6749-5p is hsa-miR-6749-5p, miR-2392 is hsa-miR-2392, miR-1273g-3p is hsa-miR-1273g-3p, miR-4746-3p is hsa-miR-4746-3p, miR-1914-3p is hsa-miR-1914-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6726-5p is hsa-miR-6726-5p, and miR-128-2-5p is hsa-miR-6726-5p. sa-miR-128-2-5p, miR-4651 is hsa-miR-4651, miR-6765-3p is hsa-miR-6765-3p, miR-3185 is hsa-miR-3185, miR-4792 is hsa-miR-4792, miR-6887-5p is hsa-miR-6887-5p, miR-5572 is hsa-miR-5572, miR-3619-3p is hsa-miR-3619-3p, miR-6780b-5p is hsa-miR-6780b-5p, miR-4707-5p is hsa-miR-4707-5p,miR-8063 is hsa-miR-8063, miR-4454 is hsa-miR-4454, miR-4525 is hsa-miR-4525, miR-7975 is hsa-miR-7975, miR-744-5p is hsa-miR-744-5p, miR-3135b is hsa-miR-3135b, miR-4648 is hsa-miR-4648, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa-miR-4741, miR-7150 is hsa-miR-7150, and miR-6791-5p is hsa-miR-6791-5p. miR-6791-5p, miR-1247-3p is hsa-miR-1247-3p, miR-7977 is hsa-miR-7977, miR-4497 is hsa-miR-4497, miR-6090 is hsa-miR-6090, miR-6781-5p is hsa-miR-6781-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4530 is hsa-miR-4530, miR-7847-3p is hsa-miR-7847-3p, miR-6825 -5p is hsa-miR-6825-5p, miR-4674 is hsa-miR-4674, miR-3917 is hsa-miR-3917, miR-4707-3p is hsa-miR-4707-3p, miR-6885-5p is hsa-miR-6885-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4516 is hsa-miR-4516, miR-6757-5p is hsa-miR-6757-5p, miR-6840-3p is hsa-miR-6840-3p, and miR-5195-3p is hsa-miR-5195-3p. 95-3p, miR-6756-5p is hsa-miR-6756-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6727-5p is hsa-miR-6727-5p, miR-6126 is hsa-miR-6126, miR-6872-3p is hsa-miR-6872-3p, miR-4446-3p is hsa-miR-4446-3p, miR-1268a is hsa-miR-1268a, miR-1908-3p is hsa-miR-1908-3p, miR-3679-5p is hsa-miR-3679-5p,miR-4534 is hsa-miR-4534, miR-4675 is hsa-miR-4675, miR-7108-5p is hsa-miR-7108-5p, miR-6799-5p is hsa-miR-6799-5p, miR-4695-5p is hsa-miR-4695-5p, miR-3178 is hsa-miR-3178, miR-5090 is hsa-miR-5090, miR-3180 is hsa-miR-3180, miR-1237-5p is hsa-miR-1237-5p, and miR-4758-5p is hsa-miR-4758-5p. 58-5p, miR-3184-5p is hsa-miR-3184-5p, miR-4286 is hsa-miR-4286, miR-6784-5p is hsa-miR-6784-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6785-5p is hsa-miR-6785-5p, miR-4706 is hsa-miR-4706, miR-711 is hsa-miR-711, miR-1260a is hsa-miR-1260a, miR-6746-5p is hsa-miR-6746-5p, miR-6089 is hsa-miR-6089 sa-miR-6089, miR-6821-5p is hsa-miR-6821-5p, miR-4667-5p is hsa-miR-4667-5p, miR-8069 is hsa-miR-8069, miR-4726-5p is hsa-miR-4726-5p, miR-6124 is hsa-miR-6124, miR-4532 is hsa-miR-4532, miR-4486 is hsa-miR-4486, miR-4728-5p is hsa-miR-4728-5p, miR-4508 is hsa-miR-4508, miR-128-1 is hsa-miR-128-1 5p is hsa-miR-128-1-5p, miR-4513 is hsa-miR-4513, miR-6795-5p is hsa-miR-6795-5p, miR-4689 is hsa-miR-4689, miR-6763-5p is hsa-miR-6763-5p, miR-8072 is hsa-miR-8072, miR-6765-5p is hsa-miR-6765-5p, miR-4419b is hsa-miR-4419b, miR-7641 is hsa-miR-7641, miR-3928-3p is hsa-miR-3928-3p,miR-1227-5p is hsa-miR-1227-5p, miR-4492 is hsa-miR-4492, miR-296-3p is hsa-miR-296-3p, miR-6769a-5p is hsa-miR-6769a-5p, miR-6889-5p is hsa-miR-6889-5p, miR-4632-5p is hsa-miR-4632-5p, miR-4505 is hsa-miR-4505, miR-3154 is hsa-miR-3154, miR-3648 is hsa-miR-3648, and miR-4442 is hsa-miR -4442, miR-3141 is hsa-miR-3141, miR-7113-3p is hsa-miR-7113-3p, miR-6819-5p is hsa-miR-6819-5p, miR-3195 is hsa-miR-3195, miR-1199-5p is hsa-miR-1199-5p, miR-6738-5p is hsa-miR-6738-5p, miR-4656 is hsa-miR-4656, miR-6820-5p is hsa-miR-6820-5p, miR-204-3p is hsa-miR-204-3p, miR-64 2a-3p is hsa-miR-642a-3p, miR-762 is hsa-miR-762, miR-1202 is hsa-miR-1202, miR-3162-5p is hsa-miR-3162-5p, miR-3196 is hsa-miR-3196, miR-3622a-5p is hsa-miR-3622a-5p, miR-3665 is hsa-miR-3665, miR-3940-5p is hsa-miR-3940-5p, miR-4294 is hsa-miR-4294, miR-4466 is hsa-miR-4466, miR-44 miR-76 is hsa-miR-4476, miR-4723-5p is hsa-miR-4723-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4730 is hsa-miR-4730, miR-4739 is hsa-miR-4739, miR-4787-5p is hsa-miR-4787-5p, miR-5787 is hsa-miR-5787, miR-6085 is hsa-miR-6085, miR-6717-5p is hsa-miR-6717-5p, miR-6724-5p is hsa-miR-6724-5p,miR-6777-5p is hsa-miR-6777-5p, miR-6778-5p is hsa-miR-6778-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6845-5p is hsa-miR-6845-5p and miR-6893-5p is hsa-miR-6893-5p. , 3. The use according to claim 1, wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a) to (e), (a) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, 580 to 606, or a base sequence in which u is t in the base sequence, and (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) under stringent conditions.
4. The use according to any one of claims 1 to 3, wherein the kit further comprises a miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, miR-575, miR-92b-5p, miR- 887-3p,miR-920,miR-1915-5p,miR-1231,miR-663b,miR-1225-5p,miR-16-5p,miR-423-5p,miR-45 1a,miR-564,miR-671-5p,miR-4763-3p,miR-3656,miR-4488,miR-125a-3p,miR-1469,miR-1228-5p, miR-6798-5p,miR-1268b,miR-6732-5p,miR-1915-3p,miR-4433b-3p,miR-1207-5p,miR-4433-3p,m iR-6879-5p,miR-4417,miR-30c-1-3p,miR-4638-5p,miR-6088,miR-4270,miR-6782-5p,miR-665,mi A nucleic acid that specifically binds to at least one of the polynucleotides among miR-486-5p, miR-4655-5p, miR-1275, miR-6806-5p, miR-614, miR-3937, miR-6752-5p, miR-6771-5p, miR-4450, miR-211-3p, miR-663a, miR-6842-5p, miR-7114-5p, and miR-6779-5p.
5. The use according to claim 4, wherein miR-615-5p is hsa-miR-615-5p, miR-486-3p is hsa-miR-486-3p, miR-1225-3p is hsa-miR-1225-3p, miR-760 is hsa-miR-760, miR-187-5p is hsa-miR-187-5p, miR-1203 is hsa-miR-1203, miR-7110-5p is hsa-miR-7110-5p, miR-371a-5p is hsa-miR-371a-5p, and miR-939-5p is hsa-miR-939-5p. p, miR-575 is hsa-miR-575, miR-92b-5p is hsa-miR-92b-5p, miR-887-3p is hsa-miR-887-3p, miR-920 is hsa-miR-920, miR-1915-5p is hsa-miR-1915-5p, miR-1231 is hsa-miR-1231, miR-663b is hsa-miR-663b, miR-1225-5p is hsa-miR-1225-5p, miR-16-5p is hsa-miR-16-5p, miR-423-5p is hsa-miR-423-5p, m iR-451a is hsa-miR-451a, miR-564 is hsa-miR-564, miR-671-5p is hsa-miR-671-5p, miR-4763-3p is hsa-miR-4763-3p, miR-3656 is hsa-miR-3656, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-1469 is hsa-miR-1469, miR-1228-5p is hsa-miR-1228-5p, miR-6798-5p is hsa-miR-6798-5p, miR-1268b is hsa-miR-1268b, miR-6732-5p is hsa-miR-6732-5p, miR-1915-3p is hsa-miR-1915-3p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1207-5p is hsa-miR-1207-5p, miR-4433-3p is hsa-miR-4433-3p, miR-6879-5p is hsa-miR-6879-5p, miR-4417 is hsa-miR-4417, miR-30c-1-3p is hsa-miR-30c-1-3p,miR-4638-5p is hsa-miR-4638-5p, miR-6088 is hsa-miR-6088, miR-4270 is hsa-miR-4270, miR-6782-5p is hsa-miR-6782-5p, miR-665 is hsa-miR-665, miR-486-5p is hsa-miR-486-5p, miR-4655-5p is hsa-miR-4655-5p, miR-1275 is hsa-miR-1275, miR-6806-5p is hsa-miR-6806-5p, miR-614 is hsa-mi R-614, miR-3937 is hsa-miR-3937, miR-6752-5p is hsa-miR-6752-5p, miR-6771-5p is hsa-miR-6771-5p, miR-4450 is hsa-miR-4450, miR-211-3p is hsa-miR-211-3p, miR-663a is hsa-miR-663a, miR-6842-5p is hsa-miR-6842-5p, miR-7114-5p is hsa-miR-7114-5p, and miR-6779-5p is hsa-miR-6779-5p. , 6. The use according to claim 4, wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (o), (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, (h) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, or a base sequence in which u is t in the base sequence, (j) a polynucleotide that hybridizes with any one of the polynucleotides (f) to (i) under stringent conditions, (k) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (l) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 153 to 187, (m) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, and (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) under stringent conditions.
7. Use of a nucleic acid capable of specifically binding to a prostate cancer marker for manufacturing a device for detecting prostate cancer, wherein the prostate cancer marker is selected from miR-3197, miR-1908-5p, miR-4257, miR-3188, miR-4649-5p, miR-1343-3p, miR-6861-5p, miR-1343-5p, miR-642b-3p, miR-6741-5p, miR-4745-5p, miR-6826-5p, miR-3663-3p, miR-3131, miR-92a-2-5p, miR-4258, miR-6125, miR-6880-5p p,miR-6132,miR-4467,miR-6749-5p,miR-2392,miR-1273g-3p,miR-4746-3p,miR-1914-3p,miR-7845-5p,miR-6726-5p,miR-128-2-5p,miR-4651, miR-6765-3p,miR-3185,miR-4792,miR-6887-5p,miR-5572,miR-3619-3p,miR-6780b-5p,miR-4707-5p,miR-8063,miR-4454,miR-4525,miR-7975,m iR-744-5p,miR-3135b,miR-4648,miR-6816-5p,miR-4741,miR-7150,miR-6791-5p,miR-1247-3p,miR-7977,miR-4497,miR-6090,miR-6781-5p,mi R-6870-5p,miR-6729-5p,miR-4530,miR-7847-3p,miR-6825-5p,miR-4674,miR-3917,miR-4707-3p,miR-6885-5p,miR-6722-3p,miR-4516,miR-675 7-5p,miR-6840-3p,miR-5195-3p,miR-6756-5p,miR-6800-5p,miR-6727-5p,miR-6126,miR-6872-3p,miR-4446-3p,miR-1268a,miR-1908-3p,miR- 3679-5p,miR-4534,miR-4675,miR-7108-5p,miR-6799-5p,miR-4695-5p,miR-3178,miR-5090,miR-3180,miR-1237-5p,miR-4758-5p,miR-3184-5p,At least one or more polynucleotides among miR-4286, miR-6784-5p, miR-6768-5p, miR-6785-5p, miR-4706, miR-711, miR-1260a, miR-6746-5p, miR-6089, miR-6821-5p, miR-4667-5p, miR-8069, miR-4726-5p, miR-6124, miR-4532, miR-4486, miR-4728-5p, miR-4508, miR-128-1-5p, miR-4513, miR-6795-5p, miR-4689, miR-6763-5p, miR-8072, miR-6765-5p, miR-4419b, miR-7641, miR-3928-3p, miR-1227-5p, miR-4492, miR-296-3p, miR-6769a-5p, miR-6889-5p, miR-4632-5p, miR-4505, miR-3154, miR-3648, miR-4442, miR-3141, miR-7113-3p, miR-6819-5p, miR-3195, miR-1199-5p, miR-6738-5p, miR-4656, miR-6820-5p, miR-204-3p, miR-642a-3p, miR-762, miR-1202, miR-3162-5p, miR-3196, miR-3622a-5p, miR-3665, miR-3940-5p, miR-4294, miR-4466, miR-4476, miR-4723-5p, miR-4725-3p, miR-4730, miR-4739, miR-4787-5p, miR-5787, miR-6085, miR-6717-5p, miR-6724-5p, miR-6777-5p, miR-6778-5p, miR-6787-5p, miR-6789-5p, miR-6845-5p, and miR-6893-5p.
8. The use according to claim 7, wherein miR-3197 is hsa-miR-3197, miR-1908-5p is hsa-miR-1908-5p, miR-4257 is hsa-miR-4257, miR-3188 is hsa-miR-3188, miR-4649-5p is hsa-miR-4649-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6861-5p is hsa-miR-6861-5p, miR-1343-5p is hsa-miR-1343-5p, and miR-642b-3p is hsa-miR-644b-3p. 2b-3p, miR-6741-5p is hsa-miR-6741-5p, miR-4745-5p is hsa-miR-4745-5p, miR-6826-5p is hsa-miR-6826-5p, miR-3663-3p is hsa-miR-3663-3p, miR-3131 is hsa-miR-3131, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4258 is hsa-miR-4258, miR-6125 is hsa-miR-6125, miR-6880-5p is hsa-miR-6880-5p, miR- 6132 is hsa-miR-6132, miR-4467 is hsa-miR-4467, miR-6749-5p is hsa-miR-6749-5p, miR-2392 is hsa-miR-2392, miR-1273g-3p is hsa-miR-1273g-3p, miR-4746-3p is hsa-miR-4746-3p, miR-1914-3p is hsa-miR-1914-3p, miR-7845-5p is hsa-miR-7845-5p, miR-6726-5p is hsa-miR-6726-5p, and miR-128-2-5p is hsa-miR-6726-5p. sa-miR-128-2-5p, miR-4651 is hsa-miR-4651, miR-6765-3p is hsa-miR-6765-3p, miR-3185 is hsa-miR-3185, miR-4792 is hsa-miR-4792, miR-6887-5p is hsa-miR-6887-5p, miR-5572 is hsa-miR-5572, miR-3619-3p is hsa-miR-3619-3p, miR-6780b-5p is hsa-miR-6780b-5p, miR-4707-5p is hsa-miR-4707-5p,miR-8063 is hsa-miR-8063, miR-4454 is hsa-miR-4454, miR-4525 is hsa-miR-4525, miR-7975 is hsa-miR-7975, miR-744-5p is hsa-miR-744-5p, miR-3135b is hsa-miR-3135b, miR-4648 is hsa-miR-4648, miR-6816-5p is hsa-miR-6816-5p, miR-4741 is hsa-miR-4741, miR-7150 is hsa-miR-7150, and miR-6791-5p is hsa-miR-6791-5p. miR-6791-5p, miR-1247-3p is hsa-miR-1247-3p, miR-7977 is hsa-miR-7977, miR-4497 is hsa-miR-4497, miR-6090 is hsa-miR-6090, miR-6781-5p is hsa-miR-6781-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6729-5p is hsa-miR-6729-5p, miR-4530 is hsa-miR-4530, miR-7847-3p is hsa-miR-7847-3p, miR-6825 -5p is hsa-miR-6825-5p, miR-4674 is hsa-miR-4674, miR-3917 is hsa-miR-3917, miR-4707-3p is hsa-miR-4707-3p, miR-6885-5p is hsa-miR-6885-5p, miR-6722-3p is hsa-miR-6722-3p, miR-4516 is hsa-miR-4516, miR-6757-5p is hsa-miR-6757-5p, miR-6840-3p is hsa-miR-6840-3p, and miR-5195-3p is hsa-miR-5195-3p. 95-3p, miR-6756-5p is hsa-miR-6756-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6727-5p is hsa-miR-6727-5p, miR-6126 is hsa-miR-6126, miR-6872-3p is hsa-miR-6872-3p, miR-4446-3p is hsa-miR-4446-3p, miR-1268a is hsa-miR-1268a, miR-1908-3p is hsa-miR-1908-3p, miR-3679-5p is hsa-miR-3679-5p,miR-4534 is hsa-miR-4534, miR-4675 is hsa-miR-4675, miR-7108-5p is hsa-miR-7108-5p, miR-6799-5p is hsa-miR-6799-5p, miR-4695-5p is hsa-miR-4695-5p, miR-3178 is hsa-miR-3178, miR-5090 is hsa-miR-5090, miR-3180 is hsa-miR-3180, miR-1237-5p is hsa-miR-1237-5p, and miR-4758-5p is hsa-miR-4758-5p. 58-5p, miR-3184-5p is hsa-miR-3184-5p, miR-4286 is hsa-miR-4286, miR-6784-5p is hsa-miR-6784-5p, miR-6768-5p is hsa-miR-6768-5p, miR-6785-5p is hsa-miR-6785-5p, miR-4706 is hsa-miR-4706, miR-711 is hsa-miR-711, miR-1260a is hsa-miR-1260a, miR-6746-5p is hsa-miR-6746-5p, miR-6089 is hsa-miR-6089 sa-miR-6089, miR-6821-5p is hsa-miR-6821-5p, miR-4667-5p is hsa-miR-4667-5p, miR-8069 is hsa-miR-8069, miR-4726-5p is hsa-miR-4726-5p, miR-6124 is hsa-miR-6124, miR-4532 is hsa-miR-4532, miR-4486 is hsa-miR-4486, miR-4728-5p is hsa-miR-4728-5p, miR-4508 is hsa-miR-4508, miR-128-1 is hsa-miR-128-1 5p is hsa-miR-128-1-5p, miR-4513 is hsa-miR-4513, miR-6795-5p is hsa-miR-6795-5p, miR-4689 is hsa-miR-4689, miR-6763-5p is hsa-miR-6763-5p, miR-8072 is hsa-miR-8072, miR-6765-5p is hsa-miR-6765-5p, miR-4419b is hsa-miR-4419b, miR-7641 is hsa-miR-7641, miR-3928-3p is hsa-miR-3928-3p,miR-1227-5p is hsa-miR-1227-5p, miR-4492 is hsa-miR-4492, miR-296-3p is hsa-miR-296-3p, miR-6769a-5p is hsa-miR-6769a-5p, miR-6889-5p is hsa-miR-6889-5p, miR-4632-5p is hsa-miR-4632-5p, miR-4505 is hsa-miR-4505, miR-3154 is hsa-miR-3154, miR-3648 is hsa-miR-3648, and miR-4442 is hsa-miR -4442, miR-3141 is hsa-miR-3141, miR-7113-3p is hsa-miR-7113-3p, miR-6819-5p is hsa-miR-6819-5p, miR-3195 is hsa-miR-3195, miR-1199-5p is hsa-miR-1199-5p, miR-6738-5p is hsa-miR-6738-5p, miR-4656 is hsa-miR-4656, miR-6820-5p is hsa-miR-6820-5p, miR-204-3p is hsa-miR-204-3p, miR-64 2a-3p is hsa-miR-642a-3p, miR-762 is hsa-miR-762, miR-1202 is hsa-miR-1202, miR-3162-5p is hsa-miR-3162-5p, miR-3196 is hsa-miR-3196, miR-3622a-5p is hsa-miR-3622a-5p, miR-3665 is hsa-miR-3665, miR-3940-5p is hsa-miR-3940-5p, miR-4294 is hsa-miR-4294, miR-4466 is hsa-miR-4466, miR-44 miR-76 is hsa-miR-4476, miR-4723-5p is hsa-miR-4723-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4730 is hsa-miR-4730, miR-4739 is hsa-miR-4739, miR-4787-5p is hsa-miR-4787-5p, miR-5787 is hsa-miR-5787, miR-6085 is hsa-miR-6085, miR-6717-5p is hsa-miR-6717-5p, miR-6724-5p is hsa-miR-6724-5p,miR-6777-5p is hsa-miR-6777-5p, miR-6778-5p is hsa-miR-6778-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6845-5p is hsa-miR-6845-5p and miR-6893-5p is hsa-miR-6893-5p. , 9. The use according to claim 7, wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a) to (e), (a) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, or 580 to 606, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 4, 2, 3, 5 to 17, 19 to 135, 580 to 606, or a base sequence in which u is t in the base sequence, and (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) under stringent conditions.
10. The use according to any one of claims 7 to 9, wherein the device further comprises a protein capable of interacting with other prostate cancer markers selected from miR-615-5p, miR-486-3p, miR-1225-3p, miR-760, miR-187-5p, miR-1203, miR-7110-5p, miR-371a-5p, miR-939-5p, miR-575, miR-92b-5p, miR- 887-3p,miR-920,miR-1915-5p,miR-1231,miR-663b,miR-1225-5p,miR-16-5p,miR-423-5p,miR-45 1a,miR-564,miR-671-5p,miR-4763-3p,miR-3656,miR-4488,miR-125a-3p,miR-1469,miR-1228-5p, miR-6798-5p,miR-1268b,miR-6732-5p,miR-1915-3p,miR-4433b-3p,miR-1207-5p,miR-4433-3p,m iR-6879-5p,miR-4417,miR-30c-1-3p,miR-4638-5p,miR-6088,miR-4270,miR-6782-5p,miR-665,m A nucleic acid that specifically binds to at least one of the polynucleotides selected from the group consisting of iR-486-5p, miR-4655-5p, miR-1275, miR-6806-5p, miR-614, miR-3937, miR-6752-5p, miR-6771-5p, miR-4450, miR-211-3p, miR-663a, miR-6842-5p, miR-7114-5p, and miR-6779-5p.
11. The use according to claim 10, wherein miR-615-5p is hsa-miR-615-5p, miR-486-3p is hsa-miR-486-3p, miR-1225-3p is hsa-miR-1225-3p, miR-760 is hsa-miR-760, miR-187-5p is hsa-miR-187-5p, miR-1203 is hsa-miR-1203, miR-7110-5p is hsa-miR-7110-5p, miR-371a-5p is hsa-miR-371a-5p, and miR-939-5p is hsa-miR-939 -5p, miR-575 is hsa-miR-575, miR-92b-5p is hsa-miR-92b-5p, miR-887-3p is hsa-miR-887-3p, miR-920 is hsa-miR-920, miR-1915-5p is hsa-miR-1915-5p, miR-1231 is hsa-miR-1231, miR-663b is hsa-miR-663b, miR-1225-5p is hsa-miR-1225-5p, miR-16-5p is hsa-miR-16-5p, miR-423-5p is hsa-miR-423-5p, miR-451a is hsa-miR-451a, miR-564 is hsa-miR-564, miR-671-5p is hsa-miR-671-5p, miR-4763-3p is hsa-miR-4763-3p, miR-3656 is hsa-miR-3656, miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-1469 is hsa-miR-1469, miR-1228-5p is hsa-miR-1228-5p, miR-6798-5p is hsa-miR-6798-5p, miR-1268b is hsa-miR-1268b, miR-6732-5p is hsa-miR-6732-5p, miR-1915-3p is hsa-miR-1915-3p, miR-4433b-3p is hsa-miR-4433b-3p, miR-1207-5p is hsa-miR-1207-5p, miR-4433-3p is hsa-miR-4433-3p, miR-6879-5p is hsa-miR-6879-5p, miR-4417 is hsa-miR-4417, miR-30c-1-3p is hsa-miR-30c-1-3p,miR-4638-5p is hsa-miR-4638-5p, miR-6088 is hsa-miR-6088, miR-4270 is hsa-miR-4270, miR-6782-5p is hsa-miR-6782-5p, miR-665 is hsa-miR-665, miR-486-5p is hsa-miR-486-5p, miR-4655-5p is hsa-miR-4655-5p, miR-1275 is hsa-miR-1275, miR-6806-5p is hsa-miR-6806-5p, miR-614 is hsa-mi R-614, miR-3937 is hsa-miR-3937, miR-6752-5p is hsa-miR-6752-5p, miR-6771-5p is hsa-miR-6771-5p, miR-4450 is hsa-miR-4450, miR-211-3p is hsa-miR-211-3p, miR-663a is hsa-miR-663a, miR-6842-5p is hsa-miR-6842-5p, miR-7114-5p is hsa-miR-7114-5p, and miR-6779-5p is hsa-miR-6779-5p. , 12. The use according to claim 10, wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (o), (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, (h) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 136 to 152 or 607 to 611, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 136 to 152 and 607 to 611, or a base sequence in which u is t in the base sequence, (j) a polynucleotide that hybridizes with any one of the polynucleotides (f) to (i) under stringent conditions, (k) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (l) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 153 to 187, (m) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 153 to 187, or a base sequence in which u is t in the base sequence, and (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) under stringent conditions.
13. The use according to any one of claims 7 to 9, wherein the device is a device for performing assays by hybridization techniques.
14. The use according to claim 13, wherein the hybridization technique is nucleic acid array technology.
