Liver cancer detection kit or device and detection method
A kit using nucleic acids that bind specifically to miRNAs like miR-1343-3p and miR-6726-5p from blood samples addresses the limitations of current liver cancer detection methods, providing a minimally invasive and highly accurate means for early detection.
Patent Information
- Application Number
- JP2025050895
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2014-06-18
- Filing Date
- 2025-03-26
- Publication Date
- 2026-02-03
- Estimated Expiration
- 2035-06-18
AI Technical Summary
Current methods for detecting liver cancer are invasive, costly, or lack sensitivity and specificity, leading to missed diagnoses and unnecessary treatments, and there is a need for a highly accurate, minimally invasive marker for early detection.
A kit comprising nucleic acids that specifically bind to miRNAs such as miR-1343-3p, miR-6726-5p, and others, allowing for the detection of liver cancer from blood samples, which can identify liver cancer patients with high accuracy and reduce the burden on patients.
The method enables early and accurate detection of liver cancer with minimal invasiveness, improving survival rates by allowing for timely treatment and reducing unnecessary tests and treatments.
Smart Images

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Figure 0007810373000082
Abstract
Description
[Technical Field]
[0001] The present invention relates to a specific method for detecting liver cancer in a subject. A kit or device for detecting liver cancer, comprising a nucleic acid capable of specifically binding to miRNA; and and a method for detecting liver cancer, which comprises measuring the expression level of the miRNA using the nucleic acid. do. [Background technology]
[0002] The liver is the largest organ in the body, located in the upper right corner of the abdomen, and its main role is to metabolize nutrients and remove harmful substances. Detoxification and excretion. Published by the National Cancer Center, Cancer Control Information Center, a national research and development organization. According to the statistics on cancer by site in Japan in 2011, the number of patients with liver cancer was 4 It is estimated that 7,271 people, or one in 35 Japanese people, will suffer from liver cancer, making it the number one cause of death. It is the sixth most common cancer site. Men are nearly twice as likely to develop the disease than women. The number of cancer deaths totaled 30,690 for both men and women, making it the fourth most common cause of cancer deaths. In addition, the estimated number of people with liver cancer in the United States in 2014 was 33,190, Of these, approximately 23,000 people are estimated to die (Non-Patent Document 1).
[0003] Generally, primary liver cancer refers to hepatocellular carcinoma, which accounts for approximately 80% of all liver cancers. In addition, there are even rarer types such as intrahepatic bile duct cancer and bile duct cystadenocarcinoma, which account for 10-20% of all primary liver cancers. There are also Nagan varieties.
[0004] The progression of liver cancer is determined in Non-Patent Document 2 by dividing it into hepatocellular carcinoma and intrahepatic bile duct cancer. In particular, hepatocellular carcinoma is classified into tumor spread (T0-4), lymph node metastasis (N0, N1) ), and depending on the degree of distant metastasis (M0, M1), stage I (T1 / N0 / M0), stage II (T1 / N0 / M0), stage III (T1 / N0 / M1), stage IV (T1 / N0 / M0 ... Stage II (T2 / N0 / M0), Stage IIIA (T3a / N0 / M0), Stage I Stage IIB (T3b / N0 / M0), Stage IIIC (T4 / N0 / M0), Stage IV It is classified as stage A (N1 / M0) or stage IVB (M1).
[0005] The 5-year relative survival rate for liver cancer varies depending on the stage of progression. 28% of localized cancers (stage 1, stage 2, and some stage 3) and 28% of cancers near the liver. 7% of cases in which adjacent metastasis is found (stage IIIC, stage IVA), and 7% of cases in which distant metastasis is found The incidence of liver cancer in patients with metastatic liver disease (stage IVB) has been reported to be 2%. If it can be detected and treated at an early stage before metastasis is observed, it will greatly contribute to improving survival rates.
[0006] Treatment for liver cancer consists of surgical treatment, mainly resection and liver transplantation, and treatment with drugs injected through puncture. The three main therapies are local therapy, which involves cauterizing the tumor to kill it, and hepatic artery embolization. These are often combined with chemotherapy and radiation therapy. If no abnormalities are observed, partial resection of the liver often results in complete recovery (Non-Patent Document 1). Even if cancer is localized, it may be difficult to detect due to factors such as the tumor's size or proximity to blood vessels. If resection is not possible, liver transplantation is recommended, and if metastasis is present, systemic chemotherapy is recommended. Chemotherapy and radiotherapy are performed (Non-patent Document 1).
[0007] As described in Non-Patent Document 1, the primary examination for liver cancer includes visual and palpation examination, as well as: There are imaging tests such as ultrasound, CT, MRI, and angiography. AFP (alpha-fetoprotein) and PIVKA as tumor markers for cancer detection -II (Pibca II) and other similar tests are known, and are often performed in conjunction with ultrasound examinations. If these primary tests reveal findings that suggest liver cancer, a secondary test is performed using a needle to examine the lesion. A pathology test is performed in which cells and tissues are collected by puncturing the skin and examined under a microscope.
[0008] On the other hand, the most important cause of liver cancer is long-term infection with hepatitis B and C viruses. Therefore, if liver cancer is suspected, in addition to the primary tests mentioned above, hepatitis virus It may also be performed in conjunction with a blood test.
[0009] Although it is still in the research stage, as shown in Patent Documents 1 to 5, it is possible to detect the effects of steroids on blood, liver tissue, and other tissues. The expression level of microRNA (miRNA) in biological samples is used to detect liver cancer. A method for this has been reported.
[0010] Patent document 1 describes the miRNAs hsa-miR-92a-3p and hsa-m iR-92b-3p, hsa-miR-92a-2-5p and hsa-miR-92b- Methods for detecting leukemia, breast cancer, and liver cancer using 5p as a marker have been demonstrated. .
[0011] Patent document 2 describes hsa-miR-23a-3p, hsa-miR-23a-3p, and hsa-miR-23a-3p contained in vesicles circulating in body fluids. sa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, h Diagnosis of various cancers using miRNAs such as sa-miR-486-3p as markers A method for doing this has been reported.
[0012] Patent Document 3 describes hsa-miR-23b-3p and hsa-miR-30 in tissues and body fluids. c-1-3p, hsa-miR-125a-3p, hsa-miR-486-3p, etc. Methods for detecting various diseases, including liver cancer, using miRNA as a marker have been demonstrated. There are.
[0013] Patent Document 4 describes hsa-miR-16-5p and hs miR-16-5p contained in vesicles circulating in body fluids. a-miR-92a-3p, hsa-miR-663a, hsa-miR-1913, h Using miRNAs such as sa-miR-625-3p and proteins as markers, Methods for detecting a variety of pathologies, including cancer, have been demonstrated.
[0014] Patent document 5 describes hsa-miR-187-5p and hsa-miR-92a-3 in plasma. p, hsa-miR-16-5p, and hsa-miR-30c-1-3p were detected in colorectal cancer and liver It has been shown to be a marker for cancer and lung cancer. [Prior art documents] [Patent documents]
[0015] [Patent Document 1] International Publication No. 2010 / 123043 [Patent Document 2] U.S. Patent Application Publication No. 2011 / 003704 [Patent Document 3] International Publication No. 2010 / 054386 [Patent Document 4] International Publication No. 2012 / 174282 [Patent Document 5] International Publication No. 2011 / 076142 [Non-patent literature]
[0016] [Non-Patent Document 1] American Cancer Society “Liver Cancer”, 2013, p.5~8, 14~15, 17~23, 27~41 [Non-patent document 2] Sobin, L. et al., “TNM Classification of Malignant Tumors 7th Edition” 2010, p.104-107 [Non-patent document 3] HCCN Guidelines "Hepato-Biliary Cancer 2nd Edition", 2014, MS-4 [Non-patent document 4] Zhang, B. and Yang, B., 1999, Journal of Medical Screening, Vol. 6(2), pp. 108-110 [Non-Patent Document 5] Takahashi, A. et al., 2008, World Journal of Gastroenterology, Vol. 14(1), pp. 129-31 Summary of the Invention [Problem to be solved by the invention]
[0017] The object of the present invention is to discover a novel liver cancer tumor marker and to develop a method for specifically binding to the marker. The present invention aims to provide a method for effectively detecting liver cancer using nucleic acids that can be used.
[0018] Liver cancer is difficult to detect early because it progresses without any noticeable symptoms. It is cancer. Also, since most of the liver is stored within the right rib cage, it is difficult to detect by palpation. Currently, for the general public who are not at risk of liver cancer due to hepatitis virus infection or cirrhosis, No effective screening method for liver cancer has been established (Non-patent Document 1). This is a widely used liver cancer screening method because it places little burden on patients and is simple. However, depending on the location of the cancer, it may be difficult to detect, and the test results may depend on the skill of the technician. Since it is highly dependent on the amount, it is recommended to use it in combination with a tumor marker (non- Patent Document 3). AFP is known as a tumor marker for detecting liver cancer. If an increase in the level is observed, liver cancer has already progressed and is unresectable or has metastasized outside the liver. In many cases, the liver cancer cells produce AFP (Non-patent Document 1). While it has been reported that AFP is not effective in cancers other than liver cancer, such as testicular cancer and ovarian cancer, It also increases in non-cancerous liver diseases, such as persistent hepatitis virus infection. It is known that markers with low specificity are known to cause catabolism (Non-Patent Document 1). For example, if other cancers are mistakenly diagnosed as liver cancer, opportunities for appropriate treatment may be missed or delayed. Applying different medical treatments may result in unnecessary financial and physical burdens on patients. In addition, a large-scale screening study of patients with hepatitis B infection and persistent hepatitis is underway. According to the results (Non-Patent Document 4), the sensitivity of AFP testing for detecting liver cancer is only 69%. However, the testing performance is insufficient for use as a screening test for liver cancer. Although tests and MRI scans are highly effective and can detect liver cancer, they require specialized equipment. The cost of the test is high, making it unsuitable for widespread use as a primary test. .
[0019] Although still in the research stage, microRNAs (miR) in biological samples such as blood There are reports on the use of the expression level of NA to distinguish liver cancer, as shown below. It has not yet been put into practical use.
[0020] Patent document 1 describes hsa-miR-92a-3p, a miRNA found in blood cells and tissues, hsa-miR-92b-3p, hsa-miR-92a-2-5p and hsa-miR A method for detecting leukemia, breast cancer, and liver cancer using -92b-5p as a marker has been presented. However, this detection method requires surgical tissue removal to obtain specimens. This process places a heavy physical burden on the patient, making it undesirable as a testing method. Furthermore, Patent Document 1 also describes the specific accuracy and sensitivity of this detection method for distinguishing liver cancer. There is no description of detection performance such as specificity, and the method is of little industrial practical use.
[0021] Patent document 2 describes hsa-miR-23a-3p, hsa-miR-23a-3p, and hsa-miR-23a-3p contained in vesicles circulating in body fluids. sa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, h Diagnosis of various cancers using miRNAs such as sa-miR-486-3p as markers However, Patent Document 2 does not provide a specific method using this detection method. There is no description of the diagnostic method for liver cancer, and the accuracy, sensitivity, and specificity of detecting liver cancer are not known. There is no description of detection performance such as the degree of sensitivity, and therefore the invention is of little industrial practical use.
[0022] Patent Document 3 describes hsa-miR-23b-3p and hsa-miR-30 in tissues and body fluids. c-1-3p, hsa-miR-125a-3p, hsa-miR-486-3p, etc. Methods for detecting various diseases, including liver cancer, using miRNA as a marker have been demonstrated. However, this detection method is based on experimental results in a mouse model, and the results in humans are unclear. Furthermore, Patent Document 3 states that the accuracy of detecting liver cancer is unclear. There is also no description of detection performance such as sensitivity and specificity, so the method is of little industrial practical use.
[0023] Patent Document 4 describes hsa-miR-16-5p and hs miR-16-5p contained in vesicles circulating in body fluids. a-miR-92a-3p, hsa-miR-663a, hsa-miR-1913, h Using miRNAs such as sa-miR-625-3p and proteins as markers, A method for detecting various pathologies, including cancer, has been disclosed. There is no description of a specific method for diagnosing liver cancer using the detection method, and NA markers have not been validated in independent specimen sets and therefore lack reliability.
[0024] Patent document 5 describes hsa-miR-187-5p and hsa-miR-92a-3 in plasma. p, hsa-miR-16-5p, and hsa-miR-30c-1-3p are associated with colorectal cancer and liver cancer. However, these markers is a marker for distinguishing a group of colon cancer from a group of liver cancer, lung cancer, and healthy subjects, It is not a marker for detecting liver cancer.
[0025] Thus, existing tumor markers have poor performance in detecting liver cancer, or The performance and detection methods of research-stage markers have not been specifically described, so these When using this method, unnecessary additional testing can be avoided by misidentifying healthy subjects as liver cancer patients. There is a possibility that treatment opportunities may be missed due to overlooking the treatment or overlooking liver cancer patients. Measuring miRNAs consisting of tens to hundreds of miRNAs increases the cost of testing, so It is difficult to use for large-scale screening such as breast cancer screening. Since extracting liver tissue for this purpose is highly invasive to the patient and undesirable, we have developed a minimally invasive method for extracting liver tissue. It can be detected from blood samples taken, and liver cancer patients can be identified, and healthy subjects can be identified. There is a need for a highly accurate liver cancer marker that can accurately distinguish liver cancer. By detecting and treating the disease, the survival rate can be improved, and partial liver resection can lead to complete recovery. Therefore, a highly sensitive liver cancer marker that can detect even low-stage liver cancer is needed. is desperately needed. [Means for solving the problem]
[0026] As a result of intensive research aimed at solving the above problems, the present inventors have discovered a method for detecting liver damage from blood that can be collected minimally invasively. We have identified several genes that can be used as cancer detection markers, and have identified nucleic acids that can specifically bind to these genes. By using the above method, it was found that liver cancer can be significantly detected. I arrived.
[0027] <Summary of the Invention> That is, the present invention has the following features.
[0028] (1) Liver cancer markers: miR-1343-3p, miR-6726-5p, and iR-6515-3p, miR-4651, miR-4257, miR-3188, mi R-6131, miR-6766-3p, miR-7641, miR-1249, miR -3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977 , miR-7110-5p, miR-6717-5p, miR-6870-5p, miR -663b, miR-6875-5p, miR-8072, miR-6816-5p, m iR-4281, miR-6729-5p, miR-8069, miR-4706, mi R-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6 857-5p, miR-1227-5p, miR-6741-5p, miR-451a miR-8063, miR-3622a-5p, miR-615-5p, miR-128 -1-5p、miR-6825-5p、miR-1260b、miR-4433-3p、 miR-4665-5p, miR-7845-5p, miR-1908-5p, miR- 6840-3p, miR-6765-5p, miR-296-5p, miR-3675- 3p, miR-6781-5p, miR-423-5p, miR-3663-3p, mi R-6784-5p, miR-6749-5p, miR-1231, miR-4746- 3p、miR-6780b-5p、miR-4758-5p、miR-3679-5p、 miR-3184-5p, miR-6125, miR-6721-5p, miR-679 1-5p, miR-3185, miR-1260a, miR-3197, miR-684 5-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p miR-4497 miR-1229-5p miR-6820-5p miR-67 77-5p, miR-3917, miR-5787, miR-4286, miR-687 7-5p, miR-1225-3p, miR-6088, miR-6800-5p, mi R-1246, miR-4467, miR-4419b, miR-1914-3p, mi R-4632-5p, miR-1915-5p, miR-3940-5p, miR-11 85-2-3p, miR-6746-5p, miR-5001-5p, miR-1228 -5p, miR-5572, miR-4327, miR-4638-5p, miR-67 99-5p, miR-6861-5p, miR-6727-5p, miR-4513, m iR-6805-3p, miR-6808-5p, miR-4449, miR-1199 -5p、miR-1275、miR-4792、miR-4443、miR-6891- 5p, miR-6826-5p, miR-6807-5p, miR-7150, miR- 4534, miR-4476, miR-4649-5p, miR-4525, miR-1 915-3p, miR-4516, miR-4417, miR-642b-3p, miR -3141, miR-5100, miR-6848-5p, miR-4739, miR- 4459、miR-1237-5p、miR-296-3p、miR-4665-3p、 miR-6786-5p, miR-4258, miR-6510-5p, miR-134 3-5p, miR-1247-3p, miR-6805-5p, miR-4492, mi R-1469, miR-1268b, miR-6858-5p, miR-3937, mi R-939-5p, miR-3656, miR-744-5p, miR-4687-3p miR-4763-3p miR-3620-5p miR-3195 miR-68 42-5p, miR-4707-5p, miR-642a-3p, miR-7113-3 p、miR-4728-5p、miR-5195-3p、miR-1185-1-3p、 miR-6774-5p, miR-8059, miR-3131, miR-7847-3 p, miR-4463, miR-128-2-5p, miR-4508, miR-680 6-5p, miR-7111-5p, miR-6782-5p, miR-4734, mi R-3162-5p, miR-887-3p, miR-6752-5p, miR-672 4-5p, miR-6757-5p, miR-4448, miR-671-5p, miR -3178, miR-4725-3p, miR-940, miR-6789-5p, mi R-4484, miR-4634, miR-4745-5p, miR-4730, miR -6803-5p, miR-6798-5p, miR-3648, miR-4783-3 At least one or more polynucleotides selected from the group consisting of miR-6836-3p and miR-6836-3p A kit for detecting liver cancer, comprising a nucleic acid capable of specifically binding to a protease inhibitor.
[0029] (2) miR-1343-3p is hsa-miR-1343-3p and miR-67 26-5p is hsa-miR-6726-5p, and miR-6515-3p is hsa -miR-6515-3p, and miR-4651 is hsa-miR-4651 , miR-4257 is hsa-miR-4257, and miR-3188 is hsa-m iR-3188, miR-6131 is hsa-miR-6131, and miR- 6766-3p is hsa-miR-6766-3p, and miR-7641 is hsa- miR-7641, miR-1249 is hsa-miR-1249, and miR -3679-3p is hsa-miR-3679-3p, and miR-6787-5p is hsa-miR-6787-5p and miR-4454 , miR-3135b is hsa-miR-3135b, and miR-6765- 3p is hsa-miR-6765-3p, and miR-7975 is hsa-miR-7 975, miR-204-3p is hsa-miR-204-3p, and miR- 7977 is hsa-miR-7977 and miR-7110-5p is hsa-miR -7110-5p, and miR-6717-5p is hsa-miR-6717-5p miR-6870-5p is hsa-miR-6870-5p, and miR-66 3b is hsa-miR-663b, and miR-6875-5p is hsa-miR-6 875-5p, miR-8072 is hsa-miR-8072, and miR-6 816-5p is hsa-miR-6816-5p, and miR-4281 is hsa-m iR-4281 and miR-6729-5p are hsa-miR-6729-5p. miR-8069 is hsa-miR-8069, and miR-4706 is hsa- miR-4706 and miR-7108-5p are hsa-miR-7108-5p. miR-4433b-3p is hsa-miR-4433b-3p, and miR- 6893-5p is hsa-miR-6893-5p, and miR-6857-5p is h sa-miR-6857-5p and miR-1227-5p are hsa-miR-12 27-5p, and miR-6741-5p is hsa-miR-6741-5p; miR-451a is hsa-miR-451a, and miR-8063 is hsa-mi R-8063, and miR-3622a-5p was found to be hsa-miR-3622a-5p. miR-615-5p is hsa-miR-615-5p, and miR-128- 1-5p is hsa-miR-128-1-5p, and miR-6825-5p is hsa -miR-6825-5p and miR-1260b are hsa-miR-1260b miR-4433-3p is hsa-miR-4433-3p, and miR-46 65-5p is hsa-miR-4665-5p, and miR-7845-5p is hsa -miR-7845-5p, and miR-1908-5p is hsa-miR-1908 -5p, miR-6840-3p is hsa-miR-6840-3p, and mi R-6765-5p is hsa-miR-6765-5p, and miR-296-5p is hsa-miR-296-5p and miR-3675-3p are hsa-miR-36 75-3p, and miR-6781-5p is hsa-miR-6781-5p; miR-423-5p is hsa-miR-423-5p, and miR-3663-3p is hsa-miR-3663-3p, and miR-6784-5p is hsa-miR- 6784-5p, and miR-6749-5p is hsa-miR-6749-5p. miR-1231 is hsa-miR-1231, and miR-4746-3p is hsa-miR-1231. sa-miR-4746-3p and miR-6780b-5p are hsa-miR-6 780b-5p, and miR-4758-5p is hsa-miR-4758-5p. miR-3679-5p is hsa-miR-3679-5p, and miR-318 4-5p is hsa-miR-3184-5p, and miR-6125 is hsa-miR -6125, and miR-6721-5p is hsa-miR-6721-5p; miR-6791-5p is hsa-miR-6791-5p, and miR-3185 is hsa-miR-3185 and miR-1260a miR-3197 is hsa-miR-3197, and miR-6845-5p is hsa-miR-6845-5p and miR-6887-5p are hsa-miR-6 887-5p, and miR-6738-5p is hsa-miR-6738-5p , miR-6872-3p is hsa-miR-6872-3p, and miR-4497 is hsa-miR-4497 and miR-1229-5p is hsa-miR-122 9-5p, miR-6820-5p is hsa-miR-6820-5p, and m iR-6777-5p is hsa-miR-6777-5p, and miR-3917 is h sa-miR-3917 and miR-5787 is hsa-miR-5787; miR-4286 is hsa-miR-4286, and miR-6877-5p is hsa -miR-6877-5p and miR-1225-3p are hsa-miR-1225 -3p, miR-6088 is hsa-miR-6088, and miR-6800 -5p is hsa-miR-6800-5p, and miR-1246 is hsa-miR- 1246, miR-4467 is hsa-miR-4467, and miR-441 9b is hsa-miR-4419b, and miR-1914-3p is hsa-miR- 1914-3p, and miR-4632-5p is hsa-miR-4632-5p. miR-1915-5p is hsa-miR-1915-5p, and miR-394 0-5p is hsa-miR-3940-5p, and miR-1185-2-3p is hs a-miR-1185-2-3p and miR-6746-5p are hsa-miR-6 746-5p, miR-5001-5p is hsa-miR-5001-5p , miR-1228-5p is hsa-miR-1228-5p, and miR-5572 is hsa-miR-5572 and miR-4327 is hsa-miR-4327 miR-4638-5p is hsa-miR-4638-5p, and miR-679 9-5p is hsa-miR-6799-5p, and miR-6861-5p is hsa- miR-6861-5p and miR-6727-5p are hsa-miR-6727- 5p, miR-4513 is hsa-miR-4513, and miR-6805- 3p is hsa-miR-6805-3p, and miR-6808-5p is hsa-mi miR-6808-5p, miR-4449 is hsa-miR-4449, and mi R-1199-5p is hsa-miR-1199-5p, and miR-1275 is hs a-miR-1275, miR-4792 is hsa-miR-4792, m iR-4443 is hsa-miR-4443, and miR-6891-5p is hsa- miR-6891-5p and miR-6826-5p are hsa-miR-6826- 5p, miR-6807-5p is hsa-miR-6807-5p, and miR -7150 is hsa-miR-7150, and miR-4534 is hsa-miR-4 534, miR-4476 is hsa-miR-4476, and miR-4649 -5p is hsa-miR-4649-5p, and miR-4525 is hsa-miR- 4525, miR-1915-3p is hsa-miR-1915-3p, and m iR-4516 is hsa-miR-4516 and miR-4417 is hsa-miR -4417, and miR-642b-3p is hsa-miR-642b-3p; miR-3141 is hsa-miR-3141 and miR-5100 is hsa-mi R-5100, and miR-6848-5p is hsa-miR-6848-5p , miR-4739 is hsa-miR-4739, and miR-4459 is hsa-m iR-4459 and miR-1237-5p are hsa-miR-1237-5p. miR-296-3p is hsa-miR-296-3p, and miR-4665- 3p is hsa-miR-4665-3p, and miR-6786-5p is hsa-mi miR-6786-5p, miR-4258 is hsa-miR-4258, and mi R-6510-5p is hsa-miR-6510-5p, and miR-1343-5p is hsa-miR-1343-5p, and miR-1247-3p is hsa-miR- 1247-3p, and miR-6805-5p is hsa-miR-6805-5p. miR-4492 is hsa-miR-4492, and miR-1469 is hsa- miR-1469, miR-1268b is hsa-miR-1268b, and m iR-6858-5p is hsa-miR-6858-5p, and miR-3937 is h sa-miR-3937 and miR-939-5p is hsa-miR-939-5p , miR-3656 is hsa-miR-3656, and miR-744-5p is hsa-miR-744-5p and miR-4687-3p are hsa-miR-46 87-3p, and miR-4763-3p is hsa-miR-4763-3p; miR-3620-5p is hsa-miR-3620-5p, and miR-3195 is hsa-miR-3195 and miR-6842-5p are hsa-miR-6842 -5p, miR-4707-5p is hsa-miR-4707-5p, and mi R-642a-3p is hsa-miR-642a-3p, and miR-7113-3p is hsa-miR-7113-3p, and miR-4728-5p is hsa-miR- 4728-5p, and miR-5195-3p is hsa-miR-5195-3p. miR-1185-1-3p is hsa-miR-1185-1-3p, and miR -6774-5p is hsa-miR-6774-5p, and miR-8059 is hsa -miR-8059, miR-3131 is hsa-miR-3131, mi R-7847-3p is hsa-miR-7847-3p, and miR-4463 is hs a-miR-4463 and miR-128-2-5p is hsa-miR-128-2 -5p, miR-4508 is hsa-miR-4508, and miR-6806 -5p is hsa-miR-6806-5p, and miR-7111-5p is hsa-m iR-7111-5p and miR-6782-5p are hsa-miR-6782-5 p, miR-4734 is hsa-miR-4734, and miR-3162-5 p is hsa-miR-3162-5p, and miR-887-3p is hsa-miR- 887-3p, and miR-6752-5p is hsa-miR-6752-5p , miR-6724-5p is hsa-miR-6724-5p, and miR-6757 -5p is hsa-miR-6757-5p, and miR-4448 is hsa-miR- 4448, miR-671-5p is hsa-miR-671-5p, and miR -3178 is hsa-miR-3178, and miR-4725-3p is hsa-mi R-4725-3p, miR-940 is hsa-miR-940, and miR- 6789-5p is hsa-miR-6789-5p, and miR-4484 is hsa- miR-4484, miR-4634 is hsa-miR-4634, and miR -4745-5p is hsa-miR-4745-5p, and miR-4730 is hsa -miR-4730 and miR-6803-5p is hsa-miR-6803-5p , miR-6798-5p is hsa-miR-6798-5p, and miR-3 648 is hsa-miR-3648, and miR-4783-3p is hsa-miR- 4783-3p, and miR-6836-3p is hsa-miR-6836-3 The kit according to (1), wherein p.
[0030] (3) The nucleic acid is a polynucleotide shown in (a) to (e) below: (a) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or the corresponding A polynucleotide consisting of a base sequence in which u is replaced by t, a variant thereof, or Derivatives or fragments thereof containing 15 or more consecutive bases, (b) a polypeptide containing a base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729; nucleotide, (c) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729 or the corresponding A polynucleotide consisting of a base sequence complementary to the base sequence in which u is t in the base sequence. , a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (d) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729 or the corresponding a polynucleotide comprising a base sequence complementary to the base sequence in which u is t in the base sequence; and (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. hybridizing polynucleotides, The kit according to (1) or (2), wherein the polynucleotide is selected from the group consisting of:
[0031] (4) The kit further comprises other liver cancer markers, such as miR-23b-3p and miR-2 3a-3p, miR-625-3p, miR-1228-3p, miR-614, miR -1913, miR-92a-2-5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3 p, miR-92b-5p, miR-92a-3p and miR-663a The nucleic acid further comprises a nucleic acid capable of specifically binding to at least one selected polynucleotide. The kit according to any one of (1) to (3).
[0032] (5) miR-23b-3p is hsa-miR-23b-3p and miR-23a- 3p is hsa-miR-23a-3p, and miR-625-3p is hsa-miR- 625-3p, miR-1228-3p is hsa-miR-1228-3p, , miR-614 is hsa-miR-614, and miR-1913 is hsa-miR -1913, and miR-92a-2-5p is hsa-miR-92a-2-5p. miR-187-5p is hsa-miR-187-5p, and miR-16-5p is hsa-miR-16-5p, and miR-92b-3p is hsa-miR-92b -3p, miR-150-3p is hsa-miR-150-3p, and miR- 564 is hsa-miR-564, and miR-125a-3p is hsa-miR-1 25a-3p, miR-92b-5p is hsa-miR-92b-5p, and m iR-92a-3p is hsa-miR-92a-3p, and miR-663a is The kit according to (4), wherein the miR-miR is hsa-miR-663a.
[0033] (6) The nucleic acid is a polynucleotide shown in (f) to (j) below: (f) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 168 to 183; (h) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (i) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. hybridizing polynucleotides, The kit according to (4) or (5), wherein the polynucleotide is selected from the group consisting of:
[0034] (7) The kit further comprises a test kit for detecting other liver cancer markers, such as miR-4688 and miR-464. 8, miR-6085, miR-6126, miR-6880-5p, miR-328- 5p, miR-6768-5p, miR-3180, miR-6087, miR-127 3g-3p, miR-1225-5p, miR-3196, miR-4695-5p, m iR-6732-5p, miR-638, miR-6813-5p, miR-665, m iR-486-3p, miR-4466, miR-30c-1-3p, miR-3621 , miR-6743-5p, miR-4298, miR-4741, miR-3619- 3p, miR-6824-5p, miR-5698, miR-371a-5p, miR- 4488, miR-1233-5p, miR-4723-5p, miR-24-3p, m iR-1238-5p, miR-4442, miR-3928-3p, miR-6716 -5p, miR-6089, miR-6124, miR-6778-5p, miR-55 At least one polynucleotide selected from the group consisting of miR-7 and miR-6090 The kit according to any one of (1) to (6), further comprising a nucleic acid capable of specifically binding to the target.
[0035] (8) miR-4688 is hsa-miR-4688 and miR-4648 is hsa -miR-4648 and miR-6085 is hsa-miR-6085, and mi R-6126 is hsa-miR-6126, and miR-6880-5p is hsa-m iR-6880-5p and miR-328-5p are hsa-miR-328-5p. miR-6768-5p is hsa-miR-6768-5p, and miR-31 80 is hsa-miR-3180 and miR-6087 is hsa-miR-6087 and miR-1273g-3p is hsa-miR-1273g-3p, and miR -1225-5p is hsa-miR-1225-5p, and miR-3196 is hsa -miR-3196 and miR-4695-5p is hsa-miR-4695-5p , miR-6732-5p is hsa-miR-6732-5p, and miR-6 38 is hsa-miR-638, and miR-6813-5p is hsa-miR-68 13-5p, miR-665 is hsa-miR-665, and miR-486- 3p is hsa-miR-486-3p, and miR-4466 is hsa-miR-44 66, miR-30c-1-3p is hsa-miR-30c-1-3p, and m iR-3621 is hsa-miR-3621, and miR-6743-5p is hsa- miR-6743-5p, miR-4298 is hsa-miR-4298, miR-4741 is hsa-miR-4741, and miR-3619-3p is hsa -miR-3619-3p and miR-6824-5p are hsa-miR-6824 -5p, miR-5698 is hsa-miR-5698, and miR-371a -5p is hsa-miR-371a-5p, and miR-4488 is hsa-miR- 4488, miR-1233-5p is hsa-miR-1233-5p, and m iR-4723-5p is hsa-miR-4723-5p, and miR-24-3p is hsa-miR-24-3p and miR-1238-5p are hsa-miR-123 8-5p, miR-4442 is hsa-miR-4442, and miR-392 8-3p is hsa-miR-3928-3p, and miR-6716-5p is hsa- miR-6716-5p, miR-6089 is hsa-miR-6089, miR-6124 is hsa-miR-6124 and miR-6778-5p is hsa -miR-6778-5p, miR-557 is hsa-miR-557, and The kit according to (7), wherein miR-6090 is hsa-miR-6090.
[0036] (9) The nucleic acid is a polynucleotide represented by any one of (k) to (o) below: (k) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 184 to 224; (m) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (n) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; hybridizing polynucleotides, The kit according to (7) or (8), wherein the polynucleotide is selected from the group consisting of:
[0037] (10) The kit includes a liver cancer marker selected from all of the liver cancer markers described in (1) or (2). At least one polynucleotide capable of specifically binding to each of at least two or more polynucleotides The kit according to any one of (1) to (9), comprising two or more nucleic acids.
[0038] (11) liver cancer markers, miR-1343-3p and miR-6726-5p; miR-6515-3p, miR-4651, miR-4257, miR-3188, m iR-6131, miR-6766-3p, miR-7641, miR-1249, mi R-3679-3p, miR-6787-5p, miR-4454, miR-3135b , miR-6765-3p, miR-7975, miR-204-3p, miR-797 7, miR-7110-5p, miR-6717-5p, miR-6870-5p, mi R-663b, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, m iR-7108-5p, miR-4433b-3p, miR-6893-5p, miR- 6857-5p, miR-1227-5p, miR-6741-5p, miR-451a , miR-8063, miR-3622a-5p, miR-615-5p, miR-12 8-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p , miR-4665-5p, miR-7845-5p, miR-1908-5p, miR -6840-3p, miR-6765-5p, miR-296-5p, miR-3675 -3p, miR-6781-5p, miR-423-5p, miR-3663-3p, m iR-6784-5p, miR-6749-5p, miR-1231, miR-4746 -3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p miR-3184-5p miR-6125 miR-6721-5p miR-67 91-5p, miR-3185, miR-1260a, miR-3197, miR-68 45-5p, miR-6887-5p, miR-6738-5p, miR-6872-3 p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6 777-5p, miR-3917, miR-5787, miR-4286, miR-68 77-5p, miR-1225-3p, miR-6088, miR-6800-5p, m iR-1246, miR-4467, miR-4419b, miR-1914-3p, m iR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1 185-2-3p, miR-6746-5p, miR-5001-5p, miR-122 8-5p, miR-5572, miR-4327, miR-4638-5p, miR-6 799-5p, miR-6861-5p, miR-6727-5p, miR-4513 miR-6805-3p, miR-6808-5p, miR-4449, miR-119 9-5p, miR-1275, miR-4792, miR-4443, miR-6891 -5p, miR-6826-5p, miR-6807-5p, miR-7150, miR -4534、miR-4476、miR-4649-5p、miR-4525、miR- 1915-3p, miR-4516, miR-4417, miR-642b-3p, mi R-3141, miR-5100, miR-6848-5p, miR-4739, miR -4459, miR-1237-5p, miR-296-3p, miR-4665-3p , miR-6786-5p, miR-4258, miR-6510-5p, miR-13 43-5p, miR-1247-3p, miR-6805-5p, miR-4492, m iR-1469, miR-1268b, miR-6858-5p, miR-3937, m iR-939-5p, miR-3656, miR-744-5p, miR-4687-3 p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6 842-5p, miR-4707-5p, miR-642a-3p, miR-7113- 3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p , miR-6774-5p, miR-8059, miR-3131, miR-7847- 3p, miR-4463, miR-128-2-5p, miR-4508, miR-68 06-5p, miR-7111-5p, miR-6782-5p, miR-4734, m iR-3162-5p, miR-887-3p, miR-6752-5p, miR-67 24-5p, miR-6757-5p, miR-4448, miR-671-5p, mi R-3178, miR-4725-3p, miR-940, miR-6789-5p, m iR-4484, miR-4634, miR-4745-5p, miR-4730, mi R-6803-5p, miR-6798-5p, miR-3648, miR-4783- At least one or more polynucleotides selected from the group consisting of miR-3p and miR-6836-3p A device for detecting liver cancer, comprising a nucleic acid capable of specifically binding to a nucleotide.
[0039] (12) miR-1343-3p is hsa-miR-1343-3p, and miR-6 726-5p is hsa-miR-6726-5p, and miR-6515-3p is hs a-miR-6515-3p, and miR-4651 is hsa-miR-4651. miR-4257 is hsa-miR-4257, and miR-3188 is hsa- miR-3188 and miR-6131 are hsa-miR-6131, and miR -6766-3p is hsa-miR-6766-3p, and miR-7641 is hsa -miR-7641, miR-1249 is hsa-miR-1249, mi R-3679-3p is hsa-miR-3679-3p, and miR-6787-5p is hsa-miR-6787-5p, and miR-4454 is hsa-miR-445 4, miR-3135b is hsa-miR-3135b, and miR-6765 -3p is hsa-miR-6765-3p, and miR-7975 is hsa-miR- 7975, miR-204-3p is hsa-miR-204-3p, and miR -7977 is hsa-miR-7977, and miR-7110-5p is hsa-mi miR-7110-5p and miR-6717-5p is hsa-miR-6717-5p , miR-6870-5p is hsa-miR-6870-5p, and miR-6 63b is hsa-miR-663b, and miR-6875-5p is hsa-miR- 6875-5p, miR-8072 is hsa-miR-8072, and miR- 6816-5p is hsa-miR-6816-5p, and miR-4281 is hsa- miR-4281 and miR-6729-5p are hsa-miR-6729-5p. miR-8069 is hsa-miR-8069, and miR-4706 is hsa -miR-4706 and miR-7108-5p is hsa-miR-7108-5p and miR-4433b-3p is hsa-miR-4433b-3p, and miR -6893-5p is hsa-miR-6893-5p, and miR-6857-5p is hsa-miR-6857-5p and miR-1227-5p are hsa-miR-1 227-5p, miR-6741-5p is hsa-miR-6741-5p , miR-451a is hsa-miR-451a, and miR-8063 is hsa-m iR-8063 and miR-3622a-5p are hsa-miR-3622a-5p , miR-615-5p is hsa-miR-615-5p, and miR-128 -1-5p is hsa-miR-128-1-5p, and miR-6825-5p is hs a-miR-6825-5p and miR-1260b is hsa-miR-1260b , miR-4433-3p is hsa-miR-4433-3p, and miR-4 665-5p is hsa-miR-4665-5p, and miR-7845-5p is hs a-miR-7845-5p and miR-1908-5p are hsa-miR-190 8-5p, miR-6840-3p is hsa-miR-6840-3p, and m iR-6765-5p is hsa-miR-6765-5p, and miR-296-5p is hsa-miR-296-5p, and miR-3675-3p is hsa-miR-3 675-3p, and miR-6781-5p is hsa-miR-6781-5p , miR-423-5p is hsa-miR-423-5p, and miR-3663-3 p is hsa-miR-3663-3p, and miR-6784-5p is hsa-miR -6784-5p, and miR-6749-5p is hsa-miR-6749-5p miR-1231 is hsa-miR-1231, and miR-4746-3p is hsa-miR-4746-3p and miR-6780b-5p are hsa-miR- 6780b-5p, and miR-4758-5p is hsa-miR-4758-5p. miR-3679-5p is hsa-miR-3679-5p, and miR-31 84-5p is hsa-miR-3184-5p, and miR-6125 is hsa-mi miR-6125, and miR-6721-5p is hsa-miR-6721-5p , miR-6791-5p is hsa-miR-6791-5p, and miR-3185 is hsa-miR-3185 and miR-1260a is hsa-miR-1260a , miR-3197 is hsa-miR-3197, and miR-6845-5p is hsa-miR-6845-5p, and miR-6887-5p is hsa-miR- 6887-5p, and miR-6738-5p is hsa-miR-6738-5p. miR-6872-3p is hsa-miR-6872-3p, and miR-449 7 is hsa-miR-4497, and miR-1229-5p is hsa-miR-12 29-5p, and miR-6820-5p is hsa-miR-6820-5p; miR-6777-5p is hsa-miR-6777-5p, and miR-3917 is hsa-miR-3917 and miR-5787 , miR-4286 is hsa-miR-4286, and miR-6877-5p is hs a-miR-6877-5p and miR-1225-3p are hsa-miR-122 5-3p, miR-6088 is hsa-miR-6088, and miR-680 0-5p is hsa-miR-6800-5p, and miR-1246 is hsa-miR -1246, miR-4467 is hsa-miR-4467, and miR-44 19b is hsa-miR-4419b, and miR-1914-3p is hsa-miR -1914-3p and miR-4632-5p are hsa-miR-4632-5p. miR-1915-5p is hsa-miR-1915-5p, and miR-39 40-5p is hsa-miR-3940-5p, and miR-1185-2-3p is h sa-miR-1185-2-3p and miR-6746-5p are hsa-miR- 6746-5p, and miR-5001-5p is hsa-miR-5001-5p. miR-1228-5p is hsa-miR-1228-5p, and miR-557 2 is hsa-miR-5572 and miR-4327 is hsa-miR-4327 miR-4638-5p is hsa-miR-4638-5p, and miR-67 99-5p is hsa-miR-6799-5p, and miR-6861-5p is hsa -miR-6861-5p, and miR-6727-5p is hsa-miR-6727 -5p, miR-4513 is hsa-miR-4513, and miR-6805 -3p is hsa-miR-6805-3p, and miR-6808-5p is hsa-m iR-6808-5p, miR-4449 is hsa-miR-4449, and m iR-1199-5p is hsa-miR-1199-5p, and miR-1275 is h sa-miR-1275 and miR-4792 is hsa-miR-4792; miR-4443 is hsa-miR-4443, and miR-6891-5p is hsa -miR-6891-5p, and miR-6826-5p is hsa-miR-6826 -5p, miR-6807-5p is hsa-miR-6807-5p, and mi R-7150 is hsa-miR-7150, and miR-4534 is hsa-miR- 4534, miR-4476 is hsa-miR-4476, and miR-464 9-5p is hsa-miR-4649-5p, and miR-4525 is hsa-miR -4525, and miR-1915-3p is hsa-miR-1915-3p, miR-4516 is hsa-miR-4516 and miR-4417 is hsa-mi R-4417, and miR-642b-3p is hsa-miR-642b-3p. , miR-3141 is hsa-miR-3141, and miR-5100 is hsa-m iR-5100 and miR-6848-5p is hsa-miR-6848-5p miR-4739 is hsa-miR-4739, and miR-4459 is hsa- miR-4459 and miR-1237-5p are hsa-miR-1237-5p. miR-296-3p is hsa-miR-296-3p, and miR-4665 -3p is hsa-miR-4665-3p, and miR-6786-5p is hsa-m iR-6786-5p, miR-4258 is hsa-miR-4258, and m iR-6510-5p is hsa-miR-6510-5p and miR-1343-5 p is hsa-miR-1343-5p and miR-1247-3p is hsa-miR -1247-3p and miR-6805-5p are hsa-miR-6805-5p. miR-4492 is hsa-miR-4492 and miR-1469 is hsa -miR-1469 and miR-1268b is hsa-miR-1268b; miR-6858-5p is hsa-miR-6858-5p, and miR-3937 is hsa-miR-3937 and miR-939-5p are hsa-miR-939-5 p, miR-3656 is hsa-miR-3656, and miR-744-5p is hsa-miR-744-5p, and miR-4687-3p is hsa-miR-4 687-3p, miR-4763-3p is hsa-miR-4763-3p , miR-3620-5p is hsa-miR-3620-5p, and miR-3195 is hsa-miR-3195 and miR-6842-5p is hsa-miR-684 2-5p, miR-4707-5p is hsa-miR-4707-5p, and m iR-642a-3p is hsa-miR-642a-3p, and miR-7113-3 p is hsa-miR-7113-3p and miR-4728-5p is hsa-miR -4728-5p, and miR-5195-3p is hsa-miR-5195-3p. miR-1185-1-3p is hsa-miR-1185-1-3p, and mi R-6774-5p is hsa-miR-6774-5p, and miR-8059 is hs a-miR-8059, miR-3131 is hsa-miR-3131, m iR-7847-3p is hsa-miR-7847-3p, and miR-4463 is h sa-miR-4463, and miR-128-2-5p is hsa-miR-128- 2-5p, miR-4508 is hsa-miR-4508, and miR-680 6-5p is hsa-miR-6806-5p, and miR-7111-5p is hsa- miR-7111-5p and miR-6782-5p are hsa-miR-6782- 5p, miR-4734 is hsa-miR-4734, and miR-3162- 5p is hsa-miR-3162-5p, and miR-887-3p is hsa-miR -887-3p, and miR-6752-5p is hsa-miR-6752-5p. miR-6724-5p is hsa-miR-6724-5p, and miR-675 7-5p is hsa-miR-6757-5p, and miR-4448 is hsa-miR -4448, miR-671-5p is hsa-miR-671-5p, and mi R-3178 is hsa-miR-3178, and miR-4725-3p is hsa-m iR-4725-3p, miR-940 is hsa-miR-940, and miR -6789-5p is hsa-miR-6789-5p, and miR-4484 is hsa -miR-4484, miR-4634 is hsa-miR-4634, and mi R-4745-5p is hsa-miR-4745-5p, and miR-4730 is hs a-miR-4730 and miR-6803-5p is hsa-miR-6803-5 p, miR-6798-5p is hsa-miR-6798-5p, and miR- 3648 is hsa-miR-3648 and miR-4783-3p is hsa-miR -4783-3p, and miR-6836-3p is hsa-miR-6836- The device according to (11), which is 3p.
[0040] (13) The nucleic acid is a polynucleotide shown in any one of (a) to (e) below: (a) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or the corresponding A polynucleotide consisting of a base sequence in which u is replaced by t, a variant thereof, or Derivatives or fragments thereof containing 15 or more consecutive bases, (b) a polypeptide containing a base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729; nucleotide, (c) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729 or the corresponding A polynucleotide consisting of a base sequence complementary to the base sequence in which u is t in the base sequence. , a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (d) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729 or the corresponding a polynucleotide comprising a base sequence complementary to the base sequence in which u is t in the base sequence; and (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. hybridizing polynucleotides, The device according to (11) or (12), which is a polynucleotide selected from the group consisting of Chair.
[0041] (14) The device is configured to detect another liver cancer marker, miR-23b-3p, miR -23a-3p, miR-625-3p, miR-1228-3p, miR-614, m iR-1913, miR-92a-2-5p, miR-187-5p, miR-16-5 p, miR-92b-3p, miR-150-3p, miR-564, miR-125a a group consisting of miR-92b-3p, miR-92b-5p, miR-92a-3p, and miR-663a and a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of: The device according to any one of (11) to (13),
[0042] (15) miR-23b-3p is hsa-miR-23b-3p, and miR-23a -3p is hsa-miR-23a-3p, and miR-625-3p is hsa-miR -625-3p, and miR-1228-3p is hsa-miR-1228-3p. miR-614 is hsa-miR-614, and miR-1913 is hsa-mi R-1913, and miR-92a-2-5p was hsa-miR-92a-2-5p. miR-187-5p is hsa-miR-187-5p, and miR-16-5 p is hsa-miR-16-5p, and miR-92b-3p is hsa-miR-92 b-3p, miR-150-3p is hsa-miR-150-3p, and miR -564 is hsa-miR-564, and miR-125a-3p is hsa-miR- 125a-3p, and miR-92b-5p is hsa-miR-92b-5p; miR-92a-3p is hsa-miR-92a-3p, and miR-663a The device according to (14), wherein the miR-1 is hsa-miR-663a.
[0043] (16) The nucleic acid is a polynucleotide shown in (f) to (j) below: (f) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 168 to 183; (h) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (i) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. hybridizing polynucleotides, The device according to (14) or (15), which is a polynucleotide selected from the group consisting of Chair.
[0044] (17) The device is capable of detecting other liver cancer markers, such as miR-4688 and miR-4 648, miR-6085, miR-6126, miR-6880-5p, miR-32 8-5p, miR-6768-5p, miR-3180, miR-6087, miR-1 273g-3p, miR-1225-5p, miR-3196, miR-4695-5p , miR-6732-5p, miR-638, miR-6813-5p, miR-665 , miR-486-3p, miR-4466, miR-30c-1-3p, miR-36 21, miR-6743-5p, miR-4298, miR-4741, miR-361 9-3p, miR-6824-5p, miR-5698, miR-371a-5p, mi R-4488, miR-1233-5p, miR-4723-5p, miR-24-3p , miR-1238-5p, miR-4442, miR-3928-3p, miR-67 16-5p, miR-6089, miR-6124, miR-6778-5p, miR- At least one or more polynucleotides selected from the group consisting of miR-557 and miR-6090 The method according to any one of (11) to (16), further comprising a nucleic acid capable of specifically binding to the nucleotide. device.
[0045] (18) miR-4688 is hsa-miR-4688 and miR-4648 is hs a-miR-4648, miR-6085 is hsa-miR-6085, m iR-6126 is hsa-miR-6126, and miR-6880-5p is hsa- miR-6880-5p and miR-328-5p are hsa-miR-328-5p , miR-6768-5p is hsa-miR-6768-5p, and miR-3 180 is hsa-miR-3180 and miR-6087 is hsa-miR-608 7, miR-1273g-3p is hsa-miR-1273g-3p, and mi R-1225-5p is hsa-miR-1225-5p, and miR-3196 is hs a-miR-3196 and miR-4695-5p is hsa-miR-4695-5 p, miR-6732-5p is hsa-miR-6732-5p, and miR- 638 is hsa-miR-638, and miR-6813-5p is hsa-miR-6 813-5p, miR-665 is hsa-miR-665, and miR-486 -3p is hsa-miR-486-3p, and miR-4466 is hsa-miR-4 466, and miR-30c-1-3p is hsa-miR-30c-1-3p; miR-3621 is hsa-miR-3621, and miR-6743-5p is hsa -miR-6743-5p, and miR-4298 is hsa-miR-4298 , miR-4741 is hsa-miR-4741, and miR-3619-3p is hs a-miR-3619-3p and miR-6824-5p are hsa-miR-682 4-5p, miR-5698 is hsa-miR-5698, and miR-371 a-5p is hsa-miR-371a-5p, and miR-4488 is hsa-miR -4488, and miR-1233-5p is hsa-miR-1233-5p; miR-4723-5p is hsa-miR-4723-5p, and miR-24-3p is hsa-miR-24-3p, and miR-1238-5p is hsa-miR-12 38-5p, miR-4442 is hsa-miR-4442, and miR-39 28-3p is hsa-miR-3928-3p, and miR-6716-5p is hsa -miR-6716-5p, and miR-6089 is hsa-miR-6089 , miR-6124 is hsa-miR-6124, and miR-6778-5p is hs a-miR-6778-5p, and miR-557 is hsa-miR-557; and the device according to (17), wherein miR-6090 is hsa-miR-6090. .
[0046] (19) The nucleic acid is a polynucleotide shown in (k) to (o) below: (k) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 184 to 224; (m) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, a variant thereof, its derivatives or fragments containing 15 or more consecutive bases; (n) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; hybridizing polynucleotides, The device according to (17) or (18), which is a polynucleotide selected from the group consisting of Chair.
[0047] (20) The device is a device for measurement by hybridization technology. The device according to any one of (11) to (19).
[0048] (21) The method according to (20), wherein the hybridization technique is a nucleic acid array technique. device.
[0049] (22) The device comprises: A small number of polynucleotides capable of specifically binding to each of at least two or more selected polynucleotides. The device according to any one of (11) to (21), comprising at least two or more nucleic acids.
[0050] (23) The kit according to any one of (1) to (10) or (11) to (22). The expression level of a target nucleic acid in a specimen of a subject is measured using the device described in The expression levels measured and the control expression levels measured in similarly healthy individuals were used to determine whether the subject had liver cancer. To evaluate in vitro whether a patient has liver cancer or not. A method for detecting liver cancer, comprising:
[0051] (24) The method according to (23), wherein the subject is a human. (25) The method according to (23) or (24), wherein the sample is blood, serum, or plasma.
[0052] <Terminology> Terms used herein have the following definitions. Nucleotide, polynucleotide, DNA, RNA, etc. are abbreviated as "base sequence" Guidelines for the Preparation of Specifications Including Sequences or Amino Acid Sequences" (edited by the Japan Patent Office) and and conventions in the art shall be followed.
[0053] As used herein, the term "polynucleotide" refers to RNA, DNA, and RNA / DNA ( The term "DNA" refers to nucleic acids that include both cDNA and chimeric DNA. The above-mentioned RNA includes total DNA, genomic DNA, and synthetic DNA. l RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA , including both non-coding RNA and synthetic RNA. As used herein, "synthetic DNA" and "synthetic RNA" refer to a DNA having a predetermined base sequence (natural sequence). or a non-natural sequence), using an automated nucleic acid synthesizer, for example. As used herein, the term "non-natural sequence" refers to DNA and RNA that have been artificially produced. and is intended to mean a sequence that differs from the native sequence, e.g., by one or more nucleotides. sequences containing substitutions, deletions, insertions and / or additions of one or more modified sequences (i.e., mutant sequences); The term "sequence" as used herein also encompasses sequences containing nucleotides (i.e., modified sequences), etc. Polynucleotide is used interchangeably with nucleic acid.
[0054] As used herein, the term "fragment" refers to a fragment having a continuous partial base sequence of a polynucleotide. It is a polynucleotide having 15 or more bases, preferably 17 or more bases, and more preferably 1 It is desirable that the length be 9 bases or more.
[0055] As used herein, the term "gene" refers not only to RNA and double-stranded DNA, but also to any of the components thereof. Each strand contains a single strand of DNA, such as the positive strand (or sense strand) or the complementary strand (or antisense strand). The term "subject matter" is intended to encompass all subjects, and is not particularly limited by its length.
[0056] Therefore, in this specification, unless otherwise specified, the term "gene" includes human genomic DNA. Double-stranded DNA, single-stranded DNA (positive strand), and single-stranded DNA with a sequence complementary to the positive strand (complementary strand, including cDNA), microRNA (miRNA), and their fragments, The term "gene" includes both a specific base sequence (or sequence number). Not only are the "genes" expressed, but the RNAs encoded by them and their biological functions are also Equivalent RNAs, e.g., homologs (i.e., homologs or orthologs), polynucleotides, The term "nucleic acid" includes "nucleic acids" that encode variants, such as homologs, variants, or derivatives. Specifically, the "nucleic acid" encoding the derivative is a nucleic acid that satisfies the stringent conditions described below. A nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence "nucleic acid" having a base sequence that hybridizes with a complementary sequence of the base sequence in which u is t "The term "gene" does not refer to any specific functional domain, and can be used to refer to any specific gene, even if it is a specific gene. For example, it may include an expression control region, a coding region, an exon, or an intron. The gene may be contained within the cell, or may be released outside the cell and exist independently. It may also be in a state encapsulated in a vesicle called an exosome.
[0057] As used herein, "exosomes" (also known as "exosomes") are molecules secreted from cells. Exosomes are small vesicles enclosed in a lipid bilayer membrane. They originate from multivesicular endosomes and are extracellular. When released into the environment, they lose internal biological substances such as genes (e.g., RNA and DNA) and proteins. Exosomes are found in bodily fluids such as blood, serum, plasma, and lymph. is known.
[0058] As used herein, the term "transcription product" refers to a RNA synthesized using the DNA sequence of a gene as a template. A refers to the region called the promoter upstream of the gene where RNA polymerase is located. and binds to the 3' end of the DNA, and binds a ribonucleotide to the 3' end so that it is complementary to the base sequence of the DNA. This RNA contains not only the gene itself but also the the region from the transcription start site to the poly(A) sequence, including the coding region, exon or intron The entire sequence is included, all the way to the termini.
[0059] In addition, in this specification, unless otherwise specified, "microRNA (miRNA)" means It is transcribed as a hairpin-like RNA precursor and has RNase III cleavage activity. It is cleaved by sRNA cleavage enzymes and incorporated into a protein complex called RISC, Non-coding RNAs of 15 to 25 bases involved in RNA translational repression are used intentionally. Furthermore, as used herein, "miRNA" is represented by a specific base sequence (or SEQ ID NO:). In addition to the miRNAs themselves, we also study the precursors of these miRNAs (pre-miRNAs, p ri-miRNAs), and miRNAs with equivalent biological functions, e.g., homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Such precursors, homologues, variants or derivatives include, in particular, miRBas e release 20 (http: / / www.mirbase.org / ) and the sequences of SEQ ID NOs: 1 to 765 can be identified under the stringent conditions described below. A base sequence that hybridizes with the complementary sequence of any specific base sequence represented by Furthermore, the term "miRNA" as used herein can be used to refer to a specific miRNA. The "miR" may be a gene product of a miR gene, and such a gene product is a mature miR. iRNA (for example, 15 to 25 bases involved in the translational repression of mRNA as described above, or 9-25 bases, non-coding RNA) or miRNA precursor (e.g., miRNAs (pre-miRNA or pri-miRNA).
[0060] As used herein, the term "probe" refers to RNA generated by gene expression or a probe derived therefrom. Polynucleotides and / or includes polynucleotides complementary thereto.
[0061] As used herein, the term "primer" refers to an RNA generated by gene expression or a primer therefor. A polynucleotide that specifically recognizes and amplifies the polynucleotide from which it is derived and / or The present invention encompasses polynucleotides complementary to the sequences of the sequences of the present invention.
[0062] Here, the complementary polynucleotide (complementary strand, reverse strand) is any one of SEQ ID NOs: 1 to 765. a base sequence defined by the above formula, or a base sequence in which u is t; The full-length sequence of a polynucleotide consisting of the above, or a partial sequence thereof (for convenience, this is referred to as the correct sequence here) base-complementary to the nucleotide sequence (called the "strand") based on base pairing relationships such as A:T(U) and G:C The term "complementary strand" refers to a polynucleotide that is in a complementary relationship to the target strand. It is not limited to cases where the base sequence is completely complementary to the target positive strand. The complementary relationship may be such that the hybridization occurs under certain conditions.
[0063] As used herein, "stringent conditions" refers to conditions under which a nucleic acid probe is highly sensitive to other sequences. to a greater extent than (e.g., the average of background measurements + the standard of background measurements) The conditions are those under which the hybridization occurs with respect to the target sequence with a standard error of at least 2 times the measured value. Stringent conditions are sequence-dependent and depend on the environment in which the hybridization occurs. The stringency of hybridization and / or washing conditions can be controlled. By doing so, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" will be described later.
[0064] As used herein, the term "Tm value" refers to the time at which the double-stranded portion of a polynucleotide is denatured into a single strand. means the temperature at which double-stranded and single-stranded molecules exist in a 1:1 ratio.
[0065] As used herein, the term "variant" refers to a naturally occurring variant of a nucleic acid resulting from polymorphism, mutation, etc. or a variant thereof, or any of the base sequences of SEQ ID NOs: 1 to 765, or In the base sequence in which u is t, or in a partial sequence thereof, one or more bases are deleted or substituted. a mutant containing a substitution, addition or insertion, or a nucleotide sequence or a partial sequence thereof, and % or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more percent identity Variants, or polynucleotides or oligonucleotides containing the base sequence or a partial sequence thereof The term "nucleotide sequence" refers to a nucleic acid that hybridizes with a target nucleic acid under stringent conditions as defined above.
[0066] As used herein, "several" refers to an integer of about 10, 9, 8, 7, 6, 5, 4, 3, or 2. means.
[0067] As used herein, the term "mutant" refers to a mutation obtained by site-directed mutagenesis or PCR. They can be produced using well-known techniques such as heterotransferase.
[0068] As used herein, "% identity" refers to the percentage of identity between proteins or sequences as determined by BLAST or FASTA as described above. using a gene search system, with or without introducing gaps, can be determined (Zheng Zhang et al., 2000, J. Comput. B iol., Vol. 7, p. 203-214; Altschul, SF et al., 1990, Jo Journal of Molecular Biology, Vol. 215, p. 403-41 0; Pearson, WR et al., 1988, Proc. Natl. Acad. Sci .USA, Vol. 85, p2444-2448).
[0069] As used herein, the term "derivative" refers to a modified nucleic acid, for example, but not limited to, labeling with a fluorophore or the like. modified nucleotides (e.g., halogenated, alkyl, such as methyl, methoxy, etc.); Reconstruction of nucleotides and bases containing alkoxy, thio, carboxymethyl, etc. groups nucleotides that have undergone double bond saturation, deamination, and substitution of oxygen molecules with sulfur molecules derivatives including PNA (peptide nucleic acid; Niels en, PE et al., 1991, Science, Vol. 254, p. 1497-500), L NA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p. 5401-5404) means.
[0070] As used herein, a polynucleotide selected from the group of miRNAs that are liver cancer markers is The "nucleic acid" capable of specifically binding to a nucleotide is a synthetic or prepared nucleic acid, specifically contains a "nucleic acid probe" or "primer" and detects the presence or absence of liver cancer in a subject or to determine whether or not a patient has liver cancer, the extent of the disease, and whether or not the patient has improved from liver cancer and the extent of improvement. To diagnose the severity and sensitivity of liver cancer to treatment, or to prevent, improve or These are used directly or indirectly to screen for candidate substances useful in therapy. These include sequences in vivo, particularly in samples of body fluids such as blood and urine, related to the onset of liver cancer. Specifically recognizes the transcription product represented by any of Nos. 1 to 765 or its cDNA synthetic nucleic acid nucleotides, oligonucleotides and polynucleotides that can bind to These nucleotides, oligonucleotides and polynucleotides have the above properties. Based on this, the above genes can be used as probes to detect the genes expressed in living organisms, tissues, cells, etc. and can be effectively used as a primer for amplifying the above gene expressed in vivo. It is possible.
[0071] The term "detection" as used herein means inspection, measurement, detection, or decision support. In addition, the term "evaluation" as used herein refers to test results or measurement results. It is used to include assisting in diagnosis or evaluation based on the above.
[0072] As used herein, a "subject" refers to a human, a primate, including a chimpanzee, a dog, a cat, or the like. Any pet animals, livestock animals such as cows, horses, sheep, goats, rodents such as mice and rats A "healthy individual" also refers to such a mammal, It means an animal that is not affected by the cancer to be detected.
[0073] As used herein, "liver cancer" refers to "primary liver cancer" that primarily occurs in the liver. For example, there are "hepatocellular carcinoma" in which liver cells have become cancerous, and "mixed hepatocytes and bile duct cells." This includes "
[0074] As used herein, "P" or "P value" refers to the probability that a statistical test will yield a positive result under the null hypothesis. indicates the probability that a statistic more extreme than the statistic calculated from the actual data will be observed. Therefore, the smaller the "P" or "P value," the more significant the difference between the compared subjects.
[0075] As used herein, "sensitivity" refers to the value of (the number of true positives) / (the number of true positives + the number of false negatives). High sensitivity means that liver cancer can be detected early and the complete cancer area can be identified. This leads to a reduction in resection and recurrence rates.
[0076] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). If the specificity is high, unnecessary additional testing due to misclassification of healthy subjects as liver cancer patients will be avoided. This will prevent the implementation of the procedure, reducing the burden on patients and cutting medical costs.
[0077] In this specification, "accuracy" means the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the percentage of all samples for which the discrimination results were correct, and is used to evaluate detection performance. This will be the first indicator.
[0078] In this specification, the term "specimen" as a target for determination, detection or diagnosis refers to a substance that can be used to detect the occurrence of liver cancer, liver The expression of the gene of the present invention changes with the progression of liver cancer and the therapeutic effect on liver cancer. Specifically, liver tissue and its surrounding blood vessels, lymph nodes, and Organs, organs suspected of metastasis, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue exudates This refers to serum and plasma prepared from blood, as well as feces, hair, etc. This refers to biological samples collected from the body, specifically genes such as RNA and miRNA.
[0079] As used herein, "hsa-miR-1343-3p gene" or "hsa-mi The term "miR-1343-3p" refers to hsa-miR-1343-3p as set forth in SEQ ID NO: 1. p gene (miRBase Accession No. MIMAT0019776) It also includes homologs or orthologs from other species. The 3p genes are described in Persson H et al., 2011, Cancer Res, vol. 71, p. 78-86. 43-3p" has a hairpin-like structure as its precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 225) is known.
[0080] As used herein, "hsa-miR-6726-5p gene" or "hsa-mi The term "miR-6726-5p" refers to hsa-miR-6726-5p as set forth in SEQ ID NO: 2. p gene (miRBase Accession No. MIMAT0027353) It also includes homologs or orthologs from other species. The 5p gene is Ladewig E et al., 2012, Genome Res, vol. 22, p. It can be obtained by the method described in 1634-1645. R-6726-5p is a precursor of hsa-mir-6, which has a hairpin-like structure. 726" (miRBase Accession No. MI0022571, SEQ ID NO: 226) is known.
[0081] As used herein, "hsa-miR-6515-3p gene" or "hsa-mi The term "miR-6515-3p" refers to hsa-miR-6515-3p as set forth in SEQ ID NO: 3. p gene (miRBase Accession No. MIMAT0025487) This includes homologs or orthologs from other species. The 3p gene is Joyce CE et al., 2011, Hum Mol Genet, vol. 20 It can be obtained by the method described in the "hsa- miR-6515-3p has a hairpin-like structure as its precursor, hsa-mir -6515" (miRBase Accession No. MI0022227, sequence Number 227) is known.
[0082] As used herein, "hsa-miR-4651 gene" or "hsa-miR-4 The term "miR-4651" refers to the hsa-miR-4651 gene (miRB) set forth in SEQ ID NO: 4. ase Accession No. MIMAT0019715) and other species homologues The hsa-miR-4651 gene is a member of the Perss On H et al., 2011, Cancer Res, Vol. 71, p. 78-86 hsa-miR-4651 can be obtained by the method described above. The miRBase Accession No. 10010062663666 forms a hairpin-like structure. ion No. MI0017279, SEQ ID NO: 228) is known.
[0083] As used herein, "hsa-miR-4257 gene" or "hsa-miR-4 The term "miR-4257" refers to the hsa-miR-4257 gene (miRB) set forth in SEQ ID NO: 5. ase Accession No. MIMAT0016878) and other species homologues The hsa-miR-4257 gene is a member of the Goff obtained by the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 In addition, "hsa-miR-4257" has a hairpin-like structure as its precursor. The structure of "hsa-mir-4257" (miRBase Accession No. .MI0015856, sequence number 229) is known.
[0084] As used herein, "hsa-miR-3188 gene" or "hsa-miR-3 The term "miR-3188" refers to the hsa-miR-3188 gene (miRB1) set forth in SEQ ID NO: 6. ase Accession No. MIMAT0015070) and other species homologues The hsa-miR-3188 gene is a member of the Stark By the method described in MS et al., 2010, PLoS One, Vol. 5, e9685 Furthermore, "hsa-miR-3188" can be obtained by using a hairpin "hsa-mir-3188" (miRBase Accession No. o.MI0014232, SEQ ID NO: 230) is known.
[0085] As used herein, "hsa-miR-6131 gene" or "hsa-miR-6 The term "miR-6131" refers to the hsa-miR-6131 gene (miRB1) set forth in SEQ ID NO: 7. ase Accession No. MIMAT0024615) and other species homologues The hsa-miR-6131 gene is a member of the Danne mann M et al., 2012, Genome Biol Evol, Vol. 4, p552-5 64. Also, "hsa-miR-6131" The precursor of miRBa is a hairpin-like structure called "hsa-mir-6131" (miRBa (Accession No. MI0021276, SEQ ID NO: 231) do.
[0086] As used herein, "hsa-miR-6766-3p gene" or "hsa-mi The term "miR-6766-3p" refers to hsa-miR-6766-3p as set forth in SEQ ID NO: 8. p gene (miRBase Accession No. MIMAT0027433) It also includes homologs or orthologs from other species. The 3p genes are described in Ladewig E et al., 2012, Genome Res, vol. 22, p. It can be obtained by the method described in 1634-1645. R-6766-3p is a precursor of hsa-mir-6, which has a hairpin-like structure. 766" (miRBase Accession No. MI0022611, SEQ ID NO: 232) is known.
[0087] As used herein, "hsa-miR-7641 gene" or "hsa-miR-7 The term "miR-7641" refers to the hsa-miR-7641 gene (miRB) set forth in SEQ ID NO: 9. ase Accession No. MIMAT0029782) and other species homologues The hsa-miR-7641 gene is a member of the Yoo J K et al., 2013, Arch Pharm Res, Vol. 36, p. 353-358 hsa-miR-7641 can be obtained by the method described above. "hsa-mir-7641-1" and "hsa-mir- 7641-2” (miRBase Accession No. MI0024975, M I0024976, SEQ ID NOs: 233, 234) are known.
[0088] As used herein, "hsa-miR-1249 gene" or "hsa-miR-1 The term "miR-1249" refers to the hsa-miR-1249 gene (miR Base Accession No. MIMAT0005901) and other species of Homo sapiens The hsa-miR-1249 gene is a member of the Mori n RD et al., 2008, Genome Res, Vol. 18, p610-621 Furthermore, "hsa-miR-1249" can be obtained by the method described above. The miRBase Accession No. 1249 (hsa-mir-1249) has a hairpin-like structure. The sequence number of the gene encoding the nucleotide sequence of the present invention is 235 (sequence number MI0006384, sequence number 235).
[0089] As used herein, "hsa-miR-3679-3p gene" or "hsa-mi The term "hsa-miR-3679-3p" refers to hsa-miR-3679- 3p gene (miRBase Accession No. MIMAT0018105) hsa-miR-3679 and other species homologs or orthologs. -3p gene, Creighton CJ et al., 2010, PLoS One, Vol. 5, The miR-36 gene can be obtained by the method described in e9637. "79-3p" has a hairpin-like structure as its precursor "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 236) is known.
[0090] As used herein, "hsa-miR-6787-5p gene" or "hsa-mi The term "miR-6787-5p" refers to hsa-miR-6787- 5p gene (miRBase Accession No. MIMAT0027474) hsa-miR-6787 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6787-5p is a precursor of the hairpin-like structure known as hsa-mir- 6787" (miRBase Accession No. MI0022632, sequence no. No. 237) is known.
[0091] As used herein, "hsa-miR-4454 gene" or "hsa-miR-4 The term "miR-4454" refers to the hsa-miR-4454 gene (miR Base Accession No. MIMAT0018976) and other species of Homo sapiens The hsa-miR-4454 gene is a member of the Jima The method described in DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4454 can be obtained as a precursor of The miRBase Accession No. 1001266666, which has an apin-like structure, is a member of the miRBase Accession No. 100126666666. n No. MI0016800, sequence number 238) is known.
[0092] As used herein, "hsa-miR-3135b gene" or "hsa-miR- The term "miR-3135b" refers to the hsa-miR-3135b gene ( miRBase Accession No. MIMAT0018985) and other organisms The hsa-miR-3135b gene includes species homologs or orthologs. Jima DD et al., 2010, Blood, vol. 116, e118-e127 hsa-miR-3135b can be obtained by the method described above. The miRBase Ac Accession No. MI0016809, SEQ ID NO: 239) is known.
[0093] As used herein, "hsa-miR-6765-3p gene" or "hsa-mi The term "miR-6765-3p" refers to hsa-miR-6765-3p as set forth in SEQ ID NO: 15. 3p gene (miRBase Accession No. MIMAT0027431) hsa-miR-6765 and other species homologs or orthologs. -3p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6765-3p is a precursor of the hairpin-like structure known as hsa-mir- 6765" (miRBase Accession No. MI0022610, sequence no. No. 240) is known.
[0094] As used herein, "hsa-miR-7975 gene" or "hsa-miR-7 The term "miR-7975" refers to the hsa-miR-7975 gene (miR Base Accession No. MIMAT0031178) and other species of Homo sapiens The hsa-miR-7975 gene is a member of the Velt family of miR-7975 genes. hut-Meikas A et al., 2013, Mol Endocrinol, online The "hsa-miR-7975" can be obtained by the method described in the above. The precursor of miRBa is “hsa-mir-7975” (miRBa (Accession No. MI0025751, SEQ ID NO: 241) do.
[0095] As used herein, "hsa-miR-204-3p gene" or "hsa-miR The term "miR-204-3p" refers to the hsa-miR-204-3p gene set forth in SEQ ID NO: 17. gene (miRBase Accession No. MIMAT0022693) and its This includes homologs or orthologs from other species. The gene is described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Furthermore, "hsa-miR-204-3p" can be obtained by the method described above. The precursor "hsa-mir-204" (miRBase Ac Accession No. MI0000284, SEQ ID NO: 242) is known.
[0096] As used herein, "hsa-miR-7977 gene" or "hsa-miR-7 The term "miR-7977" refers to the hsa-miR-7977 gene (miR Base Accession No. MIMAT0031180) and other species of Homo sapiens The hsa-miR-7977 gene is a member of the Velt hut-Meikas A et al., 2013, Mol Endocrinol, online The "hsa-miR-7977" can be obtained by the method described in the above. The precursor of miRBa is “hsa-mir-7977” (miRBa (Accession No. MI0025753, SEQ ID NO: 243) do.
[0097] As used herein, "hsa-miR-7110-5p gene" or "hsa-mi The term "miR-7110-5p" refers to hsa-miR-7110-5p as set forth in SEQ ID NO: 19. 5p gene (miRBase Accession No. MIMAT0028117) hsa-miR-7110 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-7110-5p is a precursor of the hairpin-like structure known as hsa-mir- 7110" (miRBase Accession No. MI0022961, sequence no. No. 244) is known.
[0098] As used herein, "hsa-miR-6717-5p gene" or "hsa-mi The term "miR-6717-5p" refers to hsa-miR-6717-5p as set forth in SEQ ID NO: 20. 5p gene (miRBase Accession No. MIMAT0025846) hsa-miR-6717 and other species homologs or orthologs. The -5p gene is described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. hsa-miR-6717-5p can be obtained by the method described in the literature. , and its precursor, "hsa-mir-6717" (miRBas e Accession No. MI0022551, SEQ ID NO: 245) is known .
[0099] As used herein, "hsa-miR-6870-5p gene" or "hsa-mi The term "miR-6870-5p" refers to hsa-miR-6870-5p as set forth in SEQ ID NO: 21. 5p gene (miRBase Accession No. MIMAT0027640) hsa-miR-6870 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6870-5p is a precursor of the hairpin-like structure known as hsa-mir- 6870" (miRBase Accession No. MI0022717, sequence no. No. 246) is known.
[0100] As used herein, "hsa-miR-663b gene" or "hsa-miR-6 The term "miR-663b" refers to the hsa-miR-663b gene (miR Base Accession No. MIMAT0005867) and other species of Homo sapiens The hsa-miR-663b gene is a member of the Taka da S et al., 2008, Leukemia, Vol. 22, p. 1274-1278 hsa-miR-663b can be obtained by the method described above. The miRBase Accession No. 1000012666444444444 is a miR-based gene that has a hairpin-like structure. The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0006336, sequence number 247.
[0101] As used herein, "hsa-miR-6875-5p gene" or "hsa-mi The term "miR-6875-5p" refers to hsa-miR-6875- 5p gene (miRBase Accession No. MIMAT0027650) hsa-miR-6875 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6875-5p is a precursor of the hairpin-like structure known as hsa-mir- 6875" (miRBase Accession No. MI0022722, sequence no. No. 248) is known.
[0102] As used herein, "hsa-miR-8072 gene" or "hsa-miR-8 The term "miR-8072" refers to the hsa-miR-8072 gene (miR-8072) set forth in SEQ ID NO: 24. Base Accession No. MIMAT0030999) and other species of Homo sapiens The hsa-miR-8072 gene includes genes encoding miR-1 and miR-2, and ...2 and miR-3, and includes genes encoding miR-1 and miR-4, and includes genes encoding miR-2 and miR-5, and includes genes encoding miR-1 and miR-6, and includes genes encoding miR-1 and miR-4, and includes genes encoding miR-1 and miR-5, and includes genes encoding HJ et al., 2013, Shock, Vol. 39, p. 480-487 In addition, "hsa-miR-8072" can be obtained by using hairpin as its precursor. The miRBase Accession No. 1000012444444444 has a miR-like structure. No. MI0025908, SEQ ID NO: 249) is known.
[0103] As used herein, "hsa-miR-6816-5p gene" or "hsa-mi The term "miR-6816-5p" refers to hsa-miR-6816-5p as set forth in SEQ ID NO: 25. 5p gene (miRBase Accession No. MIMAT0027532) hsa-miR-6816 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6816-5p is a precursor of the hairpin-like structure known as hsa-mir- 6816" (miRBase Accession No. MI0022661, sequence no. No. 250) is known.
[0104] As used herein, "hsa-miR-4281 gene" or "hsa-miR-4 The term "miR-4281" refers to the hsa-miR-4281 gene (miR Base Accession No. MIMAT0016907) and other species of Homo sapiens The hsa-miR-4281 gene is a Goff By the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 Furthermore, "hsa-miR-4281" can be obtained by using a hairpin "hsa-mir-4281" (miRBase Accession No. o.MI0015885, sequence number 251) is known.
[0105] As used herein, "hsa-miR-6729-5p gene" or "hsa-mi The term "miR-6729-5p" refers to hsa-miR-6729-5p as set forth in SEQ ID NO: 27. 5p gene (miRBase Accession No. MIMAT0027359) hsa-miR-6729 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6729-5p is a precursor of the hairpin-like structure known as hsa-mir- 6729" (miRBase Accession No. MI0022574, sequence no. No. 252) is known.
[0106] As used herein, "hsa-miR-8069 gene" or "hsa-miR-8 The term "miR-8069" refers to the hsa-miR-8069 gene (miR-8069) set forth in SEQ ID NO: 28. Base Accession No. MIMAT0030996) and other species of Homo sapiens The hsa-miR-8069 gene includes miR-logs, miR-1 and miR-2, and miR-3 and miR-4. HJ et al., 2013, Shock, Vol. 39, p. 480-487 In addition, "hsa-miR-8069" can be obtained by using hairpin as its precursor. The miRBase Accession No. 10000126 ... No. MI0025905, SEQ ID NO: 253) is known.
[0107] As used herein, "hsa-miR-4706 gene" or "hsa-miR-4 The term "miR-4706" refers to the hsa-miR-4706 gene (miR Base Accession No. MIMAT0019806) and other species of Homo sapiens The hsa-miR-4706 gene is a member of the Pers Son H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4706 can be obtained by the method described above. The miRBase Accession No. 10000264444444 forms a hairpin-like structure. sion No. MI0017339, SEQ ID NO: 254) is known.
[0108] As used herein, "hsa-miR-7108-5p gene" or "hsa-mi The term "hsa-miR-7108-5p" refers to hsa-miR-7108- 5p gene (miRBase Accession No. MIMAT0028113) and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-7108-5p is a precursor of the hairpin-like structure known as hsa-mir- 7108" (miRBase Accession No. MI0022959, sequence no. No. 255) is known.
[0109] As used herein, "hsa-miR-4433b-3p gene" or "hsa-m The term "miR-4433b-3p" refers to hsa-miR-443 3b-3p gene (miRBase Accession No. MIMAT00304 14) and other species homologs or orthologs. The 433b-3p gene is Ple H et al., 2012, PLoS One, Vol. 7, e50 746. b-3p" has a hairpin-like structure as its precursor, "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 256) is known.
[0110] As used herein, "hsa-miR-6893-5p gene" or "hsa-mi The term "miR-6893-5p" refers to hsa-miR-6893-5p as set forth in SEQ ID NO: 32. 5p gene (miRBase Accession No. MIMAT0027686) hsa-miR-6893 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6893-5p is a precursor of the hairpin-like structure known as hsa-mir- 6893" (miRBase Accession No. MI0022740, sequence no. No. 257) is known.
[0111] As used herein, "hsa-miR-6857-5p gene" or "hsa-mi The term "miR-6857-5p" refers to hsa-miR-6857-5p as set forth in SEQ ID NO: 33. 5p gene (miRBase Accession No. MIMAT0027614) hsa-miR-6857 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6857-5p is a precursor of the hairpin-like structure known as hsa-mir- 6857" (miRBase Accession No. MI0022703, sequence no. No. 258) is known.
[0112] As used herein, "hsa-miR-1227-5p gene" or "hsa-mi The term "miR-1227-5p" refers to hsa-miR-1227-5p as set forth in SEQ ID NO: 34. 5p gene (miRBase Accession No. MIMAT0022941) hsa-miR-1227 and other species homologs or orthologs. -5p gene, Berezikov E et al., 2007, Mol Cell, vol. 28, The miR gene can be obtained by the method described on pages 328-336. -1227-5p is a precursor of hsa-mir-12, which has a hairpin-like structure. 27" (miRBase Accession No. MI0006316, SEQ ID NO: 2 59) is known.
[0113] As used herein, "hsa-miR-6741-5p gene" or "hsa-mi The term "hsa-miR-6741-5p" refers to hsa-miR-6741-5p as set forth in SEQ ID NO: 35. 5p gene (miRBase Accession No. MIMAT0027383) hsa-miR-6741 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6741-5p is a precursor of the hairpin-like structure known as hsa-mir- 6741" (miRBase Accession No. MI0022586, sequence no. No. 260) is known.
[0114] As used herein, "hsa-miR-451a gene" or "hsa-miR-4 The term "miR-451a" refers to the hsa-miR-451a gene (miR Base Accession No. MIMAT0001631) and other species of Homo sapiens The hsa-miR-451a gene is a member of the Altu via Y et al., 2005, Nucleic Acids Res, Vol. 33, p. 2697 The miR-45 can be obtained by the method described in US Pat. No. 6,270,666. 1a” has a hairpin-like structure as its precursor “hsa-mir-451a” (mi RBase Accession No. MI0001729, sequence number 261) It is being done.
[0115] As used herein, "hsa-miR-8063 gene" or "hsa-miR-8 The term "miR-8063" refers to the hsa-miR-8063 gene (miR-8063) set forth in SEQ ID NO: 37. Base Accession No. MIMAT0030990) and other species of Homo sapiens The hsa-miR-8063 gene includes a log or ortholog. HJ et al., 2013, Shock, Vol. 39, p. 480-487 In addition, "hsa-miR-8063" can be obtained by using hairpin as its precursor. The miRBase Accession No. 10000126 ... No. MI0025899, SEQ ID NO: 262) is known.
[0116] As used herein, "hsa-miR-3622a-5p gene" or "hsa-m The term "hsa-miR-3622a-5p" refers to hsa-miR-3622a-5p as set forth in SEQ ID NO: 38. 2a-5p gene (miRBase Accession No. MIMAT00180 03) and other species homologs or orthologs. The 622a-5p gene is described in Witten D et al., 2010, BMC Biol, Vol. 8, It can be obtained by the method described in p. 58. a-5p" has a hairpin-like structure as its precursor, "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 263) is known.
[0117] As used herein, "hsa-miR-615-5p gene" or "hsa-miR The term "miR-615-5p" refers to the hsa-miR-615-5p gene set forth in SEQ ID NO: 39. gene (miRBase Accession No. MIMAT0004804) and its This includes homologs or orthologs from other species. The gene is described in Cummins JM et al., 2006, Proc Natl Acad Sci It can be obtained by the method described in USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-615-5p" has a hairpin-like structure as its precursor. Take "hsa-mir-615" (miRBase Accession No. MI0 003628, SEQ ID NO: 264) is known.
[0118] As used herein, "hsa-miR-128-1-5p gene" or "hsa-m The term "miR-128-1-5p" refers to hsa-miR-128 as set forth in SEQ ID NO: 40. -1-5p gene (miRBase Accession No. MIMAT00264 77) and other species homologs or orthologs. The 28-1-5p gene is described in Lagos-Quintana M et al., 2002, Curr It can be obtained by the method described in Biol, Vol. 12, pp. 735-739. In addition, "hsa-miR-128-1-5p" has a hairpin-like structure as its precursor. "hsa-mir-128-1" (miRBase Accession No.MI0 000447, SEQ ID NO: 265) is known.
[0119] As used herein, "hsa-miR-6825-5p gene" or "hsa-mi The term "miR-6825-5p" refers to hsa-miR-6825-5p as set forth in SEQ ID NO: 41. 5p gene (miRBase Accession No. MIMAT0027550) hsa-miR-6825 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6825-5p is a precursor of the hairpin-like structure known as hsa-mir- 6825" (miRBase Accession No. MI0022670, sequence no. No. 266) is known.
[0120] As used herein, "hsa-miR-1260b gene" or "hsa-miR- The term "miR-1260b" refers to the hsa-miR-1260b gene ( miRBase Accession No. MIMAT0015041) and other organisms The hsa-miR-1260b gene includes species homologs or orthologs. Stark MS et al., 2010, PLoS One, Vol. 5, e9685 hsa-miR-1260b can be obtained by the method described above. The miRBase Accession No. 1260b (hsa-mir-1260b) forms a hairpin-like structure. The sequence number of the gene encoding the nucleotide sequence of the present invention is 267 (sequence number MI0014197, sequence number 267).
[0121] As used herein, "hsa-miR-4433-3p gene" or "hsa-mi The term "miR-4433-3p" refers to hsa-miR-4433-3p as set forth in SEQ ID NO: 43. 3p gene (miRBase Accession No. MIMAT0018949) hsa-miR-4433 and other species homologs or orthologs. -3p gene is Jima DD et al., 2010, Blood, Vol. 116, e118-e The miR-4433 gene can be obtained by the method described in 127. -3p" has a hairpin-like structure as its precursor, "hsa-mir-4433" (m iRBase Accession No. MI0016773, sequence number 268) It is being done.
[0122] As used herein, "hsa-miR-4665-5p gene" or "hsa-mi The term "miR-4665-5p" refers to hsa-miR-4665-5p as set forth in SEQ ID NO: 44. 5p gene (miRBase Accession No. MIMAT0019739) hsa-miR-4665 and other species homologs or orthologs. -5p gene, Persson H et al., 2011, Cancer Res, vol. 71, The miR-4 gene can be obtained by the method described on pages 78-86 of this specification. 665-5p has a hairpin-like structure as its precursor, hsa-mir-4665 ” (miRBase Accession No. MI0017295, SEQ ID NO: 269 ) is known.
[0123] As used herein, "hsa-miR-7845-5p gene" or "hsa-mi The term "miR-7845-5p" refers to hsa-miR-7845-5p as set forth in SEQ ID NO: 45. 5p gene (miRBase Accession No. MIMAT0030420) hsa-miR-7845 and other species homologs or orthologs. The -5p gene is described in Ple H et al., 2012, PLoS One, Vol. 7, e50746 The "hsa-miR-7845-5p" can be obtained by the method described in the specification. The precursor of miRBa is “hsa-mir-7845” (miRBa (Accession No. MI0025515, SEQ ID NO: 270) do.
[0124] As used herein, "hsa-miR-1908-5p gene" or "hsa-mi The term "hsa-miR-1908-5p" refers to hsa-miR-1908- 5p gene (miRBase Accession No. MIMAT0007881) hsa-miR-1908 and other species homologs or orthologs. -5p gene is Bar M et al., 2008, Stem Cells, Vol. 26, p. 249 The miR-1 gene can be obtained by the method described in JP-A-2006-2505. 908-5p is a precursor of hsa-mir-1908, which has a hairpin-like structure. ” (miRBase Accession No. MI0008329, SEQ ID NO: 271 ) is known.
[0125] As used herein, "hsa-miR-6840-3p gene" or "hsa-mi The term "miR-6840-3p" refers to hsa-miR-6840-3p as set forth in SEQ ID NO: 47. 3p gene (miRBase Accession No. MIMAT0027583) and other species homologs or orthologs. -3p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6840-3p is a precursor of the hairpin-like structure known as hsa-mir- 6840" (miRBase Accession No. MI0022686, sequence no. No. 272) is known.
[0126] As used herein, "hsa-miR-6765-5p gene" or "hsa-mi The term "miR-6765-5p" refers to hsa-miR-6765-5p as set forth in SEQ ID NO: 48. 5p gene (miRBase Accession No. MIMAT0027430) hsa-miR-6765 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6765-5p is a precursor of the hairpin-like structure known as hsa-mir- 6765" (miRBase Accession No. MI0022610, sequence no. No. 240) is known.
[0127] As used herein, "hsa-miR-296-5p gene" or "hsa-miR The term "miR-296-5p" refers to the hsa-miR-296-5p gene set forth in SEQ ID NO: 49. gene (miRBase Accession No. MIMAT0000690) and its This includes homologs or orthologs from other species. The gene is Houbaviy HB et al., 2003, Dev Cell, Vol. 5, p351- 358. 5p” has a hairpin-like structure as its precursor “hsa-mir-296” (miR Base Accession No. MI0000747, SEQ ID NO: 273) is known are.
[0128] As used herein, the term "hsa-miR-3675-3p gene" or "hsa-mi The term "miR-3675-3p" refers to hsa-miR-3675- 3p gene (miRBase Accession No. MIMAT0018099) hsa-miR-3675 and other species homologs or orthologs. -3p gene is Vaz C et al., 2010, BMC Genomics, Vol. 11, p. 2 The miR-3675 gene can be obtained by the method described in 88. 3p" has a hairpin-like structure as its precursor "hsa-mir-3675" (mi RBase Accession No. MI0016076, sequence number 274) It is being done.
[0129] As used herein, "hsa-miR-6781-5p gene" or "hsa-mi The term "miR-6781-5p" refers to hsa-miR-6781-5p as set forth in SEQ ID NO: 51. 5p gene (miRBase Accession No. MIMAT0027462) hsa-miR-6781 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6781-5p is a precursor of the hairpin-like structure known as hsa-mir- 6781" (miRBase Accession No. MI0022626, sequence no. No. 275) is known.
[0130] As used herein, "hsa-miR-423-5p gene" or "hsa-miR The term "miR-423-5p" refers to the hsa-miR-423-5p gene set forth in SEQ ID NO: 52. gene (miRBase Accession No. MIMAT0004748) and its This includes homologs or orthologs from other species. The gene is described in Kasashima K et al., 2004, Biochem Biophys R It can be obtained by the method described in Es Commun, Vol. 322, p. 403-410. In addition, "hsa-miR-423-5p" has a hairpin-like structure as its precursor. The miRBase Accession No. 0001445, SEQ ID NO: 276) is known.
[0131] As used herein, "hsa-miR-3663-3p gene" or "hsa-mi The term "hsa-miR-3663-3p" refers to hsa-miR-3663- 3p gene (miRBase Accession No. MIMAT0018085) hsa-miR-3663 and other species homologs or orthologs. -3p gene, Liao JY et al., 2010, PLoS One, Vol. 5, e1056 3. Also, "hsa-miR-3663-3 p” has a hairpin-like structure as its precursor “hsa-mir-3663” (miR Base Accession No. MI0016064, SEQ ID NO: 277) is known are.
[0132] As used herein, "hsa-miR-6784-5p gene" or "hsa-mi The term "miR-6784-5p" refers to hsa-miR-6784-5p as set forth in SEQ ID NO: 54. 5p gene (miRBase Accession No. MIMAT0027468) hsa-miR-6784 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6784-5p is a precursor of the hairpin-like structure known as hsa-mir- 6784" (miRBase Accession No. MI0022629, sequence no. No. 278) is known.
[0133] As used herein, "hsa-miR-6749-5p gene" or "hsa-mi The term "miR-6749-5p" refers to hsa-miR-6749-5p as set forth in SEQ ID NO: 55. 5p gene (miRBase Accession No. MIMAT0027398) hsa-miR-6749 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6749-5p is a precursor of the hairpin-like structure known as hsa-mir- 6749" (miRBase Accession No. MI0022594, sequence no. No. 279) is known.
[0134] As used herein, "hsa-miR-1231 gene" or "hsa-miR-1 The term "miR-1231" refers to the hsa-miR-1231 gene (miR Base Accession No. MIMAT0005586) and other species of Homo sapiens The hsa-miR-1231 gene is a gene encoding a miR-1231 gene. Zikov E et al., 2007, Mol Cell, vol. 28, p328-336 hsa-miR-1231 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-1231" ( Session No. MI0006321, SEQ ID NO: 280) is known.
[0135] As used herein, "hsa-miR-4746-3p gene" or "hsa-mi The term "miR-4746-3p" refers to hsa-miR-4746-3p as set forth in SEQ ID NO: 57. 3p gene (miRBase Accession No. MIMAT0019881) hsa-miR-4746 and other species homologs or orthologs. -3p gene, Persson H et al., 2011, Cancer Res, vol. 71, The miR-4 gene can be obtained by the method described on pages 78-86 of this specification. 746-3p is a precursor of hsa-mir-4746, which has a hairpin-like structure. ” (miRBase Accession No. MI0017385, SEQ ID NO: 281 ) is known.
[0136] As used herein, "hsa-miR-6780b-5p gene" or "hsa-m The term "miR-6780b-5p" refers to hsa-miR-6780b-5p as set forth in SEQ ID NO: 58. 0b-5p gene (miRBase Accession No. MIMAT00275 72) and other species homologs or orthologs. The 780b-5p gene is from Ladewig E et al., 2012, Genome Res. It can be obtained by the method described in Vol. 22, pp. 1634-1645. sa-miR-6780b-5p has a hairpin-like structure as its precursor, hsa -mir-6780b” (miRBase Accession No. MI00226 81, SEQ ID NO: 282) is known.
[0137] As used herein, "hsa-miR-4758-5p gene" or "hsa-mi The term "miR-4758-5p" refers to hsa-miR-4758- 5p gene (miRBase Accession No. MIMAT0019903) hsa-miR-4758 and other species homologs or orthologs. -5p gene, Persson H et al., 2011, Cancer Res, vol. 71, The miR-4 gene can be obtained by the method described on pages 78-86 of this specification. 758-5p is a precursor of hsa-mir-4758, which has a hairpin-like structure. ” (miRBase Accession No. MI0017399, SEQ ID NO: 283 ) is known.
[0138] As used herein, "hsa-miR-3679-5p gene" or "hsa-mi The term "miR-3679-5p" refers to hsa-miR-3679-5p as set forth in SEQ ID NO: 60. 5p gene (miRBase Accession No. MIMAT0018104) hsa-miR-3679 and other species homologs or orthologs. -5p gene, Creighton CJ et al., 2010, PLoS One, Vol. 5, The miR-36 gene can be obtained by the method described in e9637. "79-5p" has a hairpin-like structure as its precursor "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 236) is known.
[0139] As used herein, "hsa-miR-3184-5p gene" or "hsa-mi The term "miR-3184-5p" refers to hsa-miR-3184- 5p gene (miRBase Accession No. MIMAT0015064) hsa-miR-3184 and other species homologs or orthologs. -5p gene is Stark MS et al., 2010, PLoS One, Vol. 5, e968 5. Also, "hsa-miR-3184-5 p” has a hairpin-like structure as its precursor “hsa-mir-3184” (miR Base Accession No. MI0014226, SEQ ID NO: 284) is known are.
[0140] As used herein, "hsa-miR-6125 gene" or "hsa-miR-6 The term "miR-6125" refers to the hsa-miR-6125 gene (miR-6125) set forth in SEQ ID NO: 62. Base Accession No. MIMAT0024598) and other species of Homo sapiens The hsa-miR-6125 gene is a member of the Smit h JL et al., 2012, J Virol, Vol. 86, p. 5278-5287 hsa-miR-6125 can be obtained by the method described above. The miRBase Accession No. 10000125 gene is a nucleotide sequence that forms a hairpin-like structure. sion No. MI0021259, SEQ ID NO: 285) is known.
[0141] As used herein, "hsa-miR-6721-5p gene" or "hsa-mi The term "miR-6721-5p" refers to hsa-miR-6721-5p as set forth in SEQ ID NO: 63. 5p gene (miRBase Accession No. MIMAT0025852) hsa-miR-6721 and other species homologs or orthologs. The -5p gene is described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. hsa-miR-6721-5p can be obtained by the method described in the literature. , and its precursor, "hsa-mir-6721" (miRBas e Accession No. MI0022556, SEQ ID NO: 286) is known .
[0142] As used herein, "hsa-miR-6791-5p gene" or "hsa-mi The term "miR-6791-5p" refers to hsa-miR-6791-5p as set forth in SEQ ID NO: 64. 5p gene (miRBase Accession No. MIMAT0027482) hsa-miR-6791 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6791-5p is a precursor of the hairpin-like structure known as hsa-mir- 6791" (miRBase Accession No. MI0022636, sequence no. No. 287) is known.
[0143] As used herein, "hsa-miR-3185 gene" or "hsa-miR-3 The term "miR-3185" refers to the hsa-miR-3185 gene (miR-3185) set forth in SEQ ID NO: 65. Base Accession No. MIMAT0015065) and other species of Homo sapiens The hsa-miR-3185 gene is a member of the Star By the method described in k MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3185" can be obtained by using hairpin as its precursor. The miRBase Accession No. 1000012666666 (hsa-mir-3185) has a miR-like structure. No. MI0014227, SEQ ID NO: 288) are known.
[0144] As used herein, "hsa-miR-1260a gene" or "hsa-miR- The term "miR-1260a" refers to the hsa-miR-1260a gene ( miRBase Accession No. MIMAT0005911) and other organisms The hsa-miR-1260a gene includes species homologs or orthologs. Morin RD et al., 2008, Genome Res, Vol. 18, p. 610-621 hsa-miR-1260a can be obtained by the method described in Its precursor, "hsa-mir-1260a" (miRBas e Accession No. MI0006394, SEQ ID NO: 289) is known .
[0145] As used herein, "hsa-miR-3197 gene" or "hsa-miR-3 The term "miR-3197" refers to the hsa-miR-3197 gene (miR Base Accession No. MIMAT0015082) and other species of Homo sapiens The hsa-miR-3197 gene is a member of the Star By the method described in k MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3197" can be obtained by using hairpin as its precursor. The miRBase Accession No. 100001266664 (hsa-mir-3197) has a phosphodiesterase-like structure. No. MI0014245, SEQ ID NO: 290) is known.
[0146] As used herein, "hsa-miR-6845-5p gene" or "hsa-mi The term "miR-6845-5p" refers to hsa-miR-6845-5p as set forth in SEQ ID NO: 68. 5p gene (miRBase Accession No. MIMAT0027590) hsa-miR-6845 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6845-5p is a precursor of the hairpin-like structure known as hsa-mir- 6845" (miRBase Accession No. MI0022691, sequence no. No. 291) is known.
[0147] As used herein, "hsa-miR-6887-5p gene" or "hsa-mi The term "miR-6887-5p" refers to hsa-miR-6887- 5p gene (miRBase Accession No. MIMAT0027674) hsa-miR-6887 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6887-5p is a precursor of the hairpin-like structure known as hsa-mir- 6887" (miRBase Accession No. MI0022734, sequence no. No. 292) is known.
[0148] As used herein, "hsa-miR-6738-5p gene" or "hsa-mi The term "miR-6738-5p" refers to hsa-miR-6738-5p as set forth in SEQ ID NO: 70. 5p gene (miRBase Accession No. MIMAT0027377) and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6738-5p is a precursor of the hairpin-like structure known as hsa-mir- 6738" (miRBase Accession No. MI0022583, sequence no. No. 293) is known.
[0149] As used herein, "hsa-miR-6872-3p gene" or "hsa-mi The term "miR-6872-3p" refers to hsa-miR-6872-3p as set forth in SEQ ID NO: 71. 3p gene (miRBase Accession No. MIMAT0027645) hsa-miR-6872 and other species homologs or orthologs. -3p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6872-3p is a precursor of the hairpin-like structure known as hsa-mir- 6872" (miRBase Accession No. MI0022719, sequence no. No. 294) is known.
[0150] As used herein, "hsa-miR-4497 gene" or "hsa-miR-4 The term "miR-4497" refers to the hsa-miR-4497 gene (miR Base Accession No. MIMAT0019032) and other species of Homo sapiens The hsa-miR-4497 gene is a member of the Jima The method described in DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4497 can be obtained by The apin-like structure of "hsa-mir-4497" (miRBase Accession No. n No. MI0016859, sequence number 295) is known.
[0151] As used herein, "hsa-miR-1229-5p gene" or "hsa-mi The term "miR-1229-5p" refers to hsa-miR-1229-5p as set forth in SEQ ID NO: 73. 5p gene (miRBase Accession No. MIMAT0022942) hsa-miR-1229 and other species homologs or orthologs. -5p gene, Berezikov E et al., 2007, Mol Cell, vol. 28, The miR gene can be obtained by the method described on pages 328-336. -1229-5p is a precursor of hsa-mir-12, which has a hairpin-like structure. 29" (miRBase Accession No. MI0006319, SEQ ID NO: 2 96) is known.
[0152] As used herein, "hsa-miR-6820-5p gene" or "hsa-mi The term "miR-6820-5p" refers to hsa-miR-6820-5p as set forth in SEQ ID NO: 74. 5p gene (miRBase Accession No. MIMAT0027540) hsa-miR-6820 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6820-5p is a precursor of the hairpin-like structure known as hsa-mir- 6820" (miRBase Accession No. MI0022665, sequence no. No. 297) is known.
[0153] As used herein, "hsa-miR-6777-5p gene" or "hsa-mi The term "miR-6777-5p" refers to hsa-miR-6777-5p as set forth in SEQ ID NO: 75. 5p gene (miRBase Accession No. MIMAT0027454) hsa-miR-6777 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6777-5p is a precursor of the hairpin-like structure known as hsa-mir- 6777" (miRBase Accession No. MI0022622, sequence no. No. 298) is known.
[0154] As used herein, "hsa-miR-3917 gene" or "hsa-miR-3 The term "miR-3917" refers to the hsa-miR-3917 gene (miR Base Accession No. MIMAT0018191) and other species of Homo sapiens The hsa-miR-3917 gene is a gene encoding a miR-3917 gene. As described in ghton CJ et al., 2010, PLoS One, Vol. 5, e9637 hsa-miR-3917 can be obtained by the method described above. The miRBase Accession No. 1000020 ... ion No. MI0016423, SEQ ID NO: 299) is known.
[0155] As used herein, "hsa-miR-5787 gene" or "hsa-miR-5 The term "miR-5787" refers to the hsa-miR-5787 gene (miR Base Accession No. MIMAT0023252) and other species of Homo sapiens The hsa-miR-5787 gene is a member of the Yoo H et al., 2011, Biochem Biophys Res Commun, vol. 415 It can be obtained by the method described in the "hsa-mi" R-5787 has a hairpin-like structure as its precursor, hsa-mir-5787 ” (miRBase Accession No. MI0019797, SEQ ID NO: 300 ) is known.
[0156] As used herein, "hsa-miR-4286 gene" or "hsa-miR-4 The term "miR-4286" refers to the hsa-miR-4286 gene (miR Base Accession No. MIMAT0016916) and other species of Homo sapiens The hsa-miR-4286 gene is a member of the Goff By the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 Furthermore, "hsa-miR-4286" can be obtained by using a hairpin The miRBase Accession No. 100001266444444 has a similar structure to "hsa-mir-4286" (miRBase Accession No. 1000012664 ...). o.MI0015894, sequence number 301) is known.
[0157] As used herein, "hsa-miR-6877-5p gene" or "hsa-mi The term "miR-6877-5p" refers to hsa-miR-6877- 5p gene (miRBase Accession No. MIMAT0027654) hsa-miR-6877 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6877-5p is a precursor of the hairpin-like structure known as hsa-mir- 6877" (miRBase Accession No. MI0022724, sequence no. No. 302) is known.
[0158] As used herein, "hsa-miR-1225-3p gene" or "hsa-mi The term "miR-1225-3p" refers to hsa-miR-1225-3p as set forth in SEQ ID NO: 80. 3p gene (miRBase Accession No. MIMAT0005573) hsa-miR-1225 and other species homologs or orthologs. -3p gene, Berezikov E et al., 2007, Mol Cell, vol. 28, The miR gene can be obtained by the method described on pages 328-336. -1225-3p is a precursor of hsa-mir-12, which has a hairpin-like structure. 25" (miRBase Accession No. MI0006311, SEQ ID NO: 3 03) is known.
[0159] As used herein, "hsa-miR-6088 gene" or "hsa-miR-6 The term "miR-6088" refers to the hsa-miR-6088 gene (miR-6088) set forth in SEQ ID NO: 81. Base Accession No. MIMAT0023713) and other species of Homo sapiens The hsa-miR-6088 gene is a member of the Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057 hsa-miR-6088 can be obtained by the method described in The precursor of the hairpin-like structure "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 304) is known.
[0160] As used herein, "hsa-miR-6800-5p gene" or "hsa-mi The term "miR-6800-5p" refers to hsa-miR-6800-5p as set forth in SEQ ID NO: 82. 5p gene (miRBase Accession No. MIMAT0027500) hsa-miR-6800 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6800-5p is a precursor of the hairpin-like structure known as hsa-mir- 6800" (miRBase Accession No. MI0022645, sequence no. No. 305) is known.
[0161] As used herein, "hsa-miR-1246 gene" or "hsa-miR-1 The term "miR-1246" refers to the hsa-miR-1246 gene (miR-1246) set forth in SEQ ID NO: 83. Base Accession No. MIMAT0005898) and other species of Homo sapiens The hsa-miR-1246 gene is a member of the Mori n RD et al., 2008, Genome Res, Vol. 18, p610-621 Furthermore, "hsa-miR-1246" can be obtained by the method described above. The miRBase Accession No. 1246 (hsa-mir-1246) has a hairpin-like structure. The sequence number of the nucleotide sequence ...
[0162] As used herein, "hsa-miR-4467 gene" or "hsa-miR-4 The term "miR-4467" refers to the hsa-miR-4467 gene (miR Base Accession No. MIMAT0018994) and other species of Homo sapiens The hsa-miR-4467 gene is a member of the Jima The method described in DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4467 can be obtained by The apin-like structure of "hsa-mir-4467" (miRBase Accession No. 1001001001001) n No. MI0016818, sequence number 307) is known.
[0163] As used herein, "hsa-miR-4419b gene" or "hsa-miR- The term "miR-4419b" refers to the hsa-miR-4419b gene set forth in SEQ ID NO: 85 ( miRBase Accession No. MIMAT0019034) and other organisms The hsa-miR-4419b gene includes species homologs or orthologs. Jima DD et al., 2010, Blood, vol. 116, e118-e127 hsa-miR-4419b can be obtained by the method described above. The miRBase Ac Accession No. MI0016861, SEQ ID NO: 308) is known.
[0164] As used herein, "hsa-miR-1914-3p gene" or "hsa-mi The term "hsa-miR-1914-3p" refers to hsa-miR-1914- 3p gene (miRBase Accession No. MIMAT0007890) hsa-miR-1914 and other species homologs or orthologs. -3p gene is Bar M et al., 2008, Stem Cells, Vol. 26, p. 249 The miR-1 gene can be obtained by the method described in JP-A-2006-2505. 914-3p is a precursor of hsa-mir-1914, which has a hairpin-like structure. ” (miRBase Accession No. MI0008335, SEQ ID NO: 309 ) is known.
[0165] As used herein, "hsa-miR-4632-5p gene" or "hsa-mi The term "miR-4632-5p" refers to hsa-miR-4632-5p as set forth in SEQ ID NO: 87. 5p gene (miRBase Accession No. MIMAT0022977) hsa-miR-4632 and other species homologs or orthologs. -5p gene, Persson H et al., 2011, Cancer Res, vol. 71, The miR-4 gene can be obtained by the method described on pages 78-86 of this specification. 632-5p has a hairpin-like structure as its precursor, hsa-mir-4632 ” (miRBase Accession No. MI0017259, SEQ ID NO: 310 ) is known.
[0166] As used herein, "hsa-miR-1915-5p gene" or "hsa-mi The term "hsa-miR-1915-5p" refers to hsa-miR-1915- 5p gene (miRBase Accession No. MIMAT0007891) hsa-miR-1915 and other species homologs or orthologs. -5p gene is Bar M et al., 2008, Stem Cells, Vol. 26, p. 249 The miR-1 gene can be obtained by the method described in JP-A-2006-2505. 915-5p has a hairpin-like structure as its precursor, hsa-mir-1915 ” (miRBase Accession No. MI0008336, SEQ ID NO: 311 ) is known.
[0167] As used herein, "hsa-miR-3940-5p gene" or "hsa-mi The term "miR-3940-5p" refers to hsa-miR-3940-5p as set forth in SEQ ID NO: 89. 5p gene (miRBase Accession No. MIMAT0019229) and other species homologs or orthologs. -5p gene, Liao JY et al., 2010, PLoS One, Vol. 5, e1056 The miR-3940-5 gene can be obtained by the method described in 3. p” has a hairpin-like structure as its precursor “hsa-mir-3940” (miR Base Accession No. MI0016597, SEQ ID NO: 312) is known are.
[0168] As used herein, "hsa-miR-1185-2-3p gene" or "hsa- The term "miR-1185-2-3p" refers to hsa-miR-1 as set forth in SEQ ID NO: 90. 185-2-3p gene (miRBase Accession No. MIMAT00 22713) and other species homologs or orthologs. The R-1185-2-3p gene was identified in Berezikov E et al., 2006, Genom e Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-1185-2-3p" has a hairpin-like structure as its precursor. The miRBase Accession No. .MI0003821, sequence number 313) is known.
[0169] As used herein, "hsa-miR-6746-5p gene" or "hsa-mi The term "miR-6746-5p" refers to hsa-miR-6746-5p as set forth in SEQ ID NO: 91. 5p gene (miRBase Accession No. MIMAT0027392) and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6746-5p is a precursor of the hairpin-like structure known as hsa-mir- 6746" (miRBase Accession No. MI0022591, sequence no. No. 314) is known.
[0170] As used herein, "hsa-miR-5001-5p gene" or "hsa-mi The term "hsa-miR-5001-5p" refers to hsa-miR-5001-5p as set forth in SEQ ID NO: 92. 5p gene (miRBase Accession No. MIMAT0021021) hsa-miR-5001 and other species homologs or orthologs. -5p gene is Hansen TB et al., 2011, RNA Biol, Vol. 8, p. 37 The "hsa-miR-50" can be obtained by the method described in JP-A-2008-383. "01-5p" has a hairpin-like structure as its precursor "hsa-mir-5001" (miRBase Accession No. MI0017867, SEQ ID NO: 315) is known.
[0171] As used herein, "hsa-miR-1228-5p gene" or "hsa-mi The term "miR-1228-5p" refers to hsa-miR-1228-5p as set forth in SEQ ID NO: 93. 5p gene (miRBase Accession No. MIMAT0005582) hsa-miR-1228 and other species homologs or orthologs. -5p gene, Berezikov E et al., 2007, Mol Cell, vol. 28, The miR gene can be obtained by the method described on pages 328-336. -1228-5p is a precursor of hsa-mir-12, which has a hairpin-like structure. 28" (miRBase Accession No. MI0006318, SEQ ID NO: 3 16) is known.
[0172] As used herein, "hsa-miR-5572 gene" or "hsa-miR-5 The term "miR-5572" refers to the hsa-miR-5572 gene (miR Base Accession No. MIMAT0022260) and other species of Homo sapiens The hsa-miR-5572 gene is a member of the Tand On M et al., 2012, Oral Dis, Vol. 18, p. 127-131 hsa-miR-5572 can be obtained by the method described above. The miRBase Accession No. 10022666664 (hsa-mir-5572) forms a hairpin-like structure. ion No. MI0019117, SEQ ID NO: 317) is known.
[0173] As used herein, "hsa-miR-4327 gene" or "hsa-miR-4 The term "miR-4327" refers to the hsa-miR-4327 gene (miR Base Accession No. MIMAT0016889) and other species of Homo sapiens The hsa-miR-4327 gene is a Goff By the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 Furthermore, "hsa-miR-4327" can be obtained by using a hairpin The miRBase Accession No. 10000126634444 has a similar structure to "hsa-mir-4327" (miRBase Accession No. 100001266344444). o.MI0015867, SEQ ID NO: 318) is known.
[0174] As used herein, "hsa-miR-4638-5p gene" or "hsa-mi The term "miR-4638-5p" refers to hsa-miR-4638-5p as set forth in SEQ ID NO: 96. 5p gene (miRBase Accession No. MIMAT0019695) hsa-miR-4638 and other species homologs or orthologs. -5p gene, Persson H et al., 2011, Cancer Res, vol. 71, The miR-4 gene can be obtained by the method described on pages 78-86 of this specification. 638-5p has a hairpin-like structure as its precursor, hsa-mir-4638 ” (miRBase Accession No. MI0017265, SEQ ID NO: 319 ) is known.
[0175] As used herein, "hsa-miR-6799-5p gene" or "hsa-mi The term "miR-6799-5p" refers to hsa-miR-6799-5p as set forth in SEQ ID NO: 97. 5p gene (miRBase Accession No. MIMAT0027498) hsa-miR-6799 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6799-5p is a precursor of the hairpin-like structure known as hsa-mir- 6799" (miRBase Accession No. MI0022644, sequence no. No. 320) is known.
[0176] As used herein, "hsa-miR-6861-5p gene" or "hsa-mi The term "hsa-miR-6861-5p" refers to hsa-miR-6861-5p as set forth in SEQ ID NO: 98. 5p gene (miRBase Accession No. MIMAT0027623) hsa-miR-6861 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6861-5p is a precursor of the hairpin-like structure known as hsa-mir- 6861" (miRBase Accession No. MI0022708, sequence no. No. 321) is known.
[0177] As used herein, "hsa-miR-6727-5p gene" or "hsa-mi The term "miR-6727-5p" refers to hsa-miR-6727-5p as set forth in SEQ ID NO: 99. 5p gene (miRBase Accession No. MIMAT0027355) hsa-miR-6727 and other species homologs or orthologs. -5p gene, Ladewig E et al., 2012, Genome Res, vol. 22, It can be obtained by the method described on pages 1634-1645. iR-6727-5p is a precursor of the hairpin-like structure known as hsa-mir- 6727" (miRBase Accession No. MI0022572, sequence no. No. 322) is known.
[0178] As used herein, "hsa-miR-4513 gene" or "hsa-miR-4 The term "miR-4513" refers to the hsa-miR-4513 gene (miR-4513) set forth in SEQ ID NO: 100. RBase Accession No. MIMAT0019050) and other species The hsa-miR-4513 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 In addition, "hsa-miR-4513" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4513" (miRBase Accession No. on No. MI0016879, SEQ ID NO: 323) is known.
[0179] As used herein, "hsa-miR-6805-3p gene" or "hsa-mi The term "miR-6805-3p" refers to hsa-miR-6805 as set forth in SEQ ID NO: 101. -3p gene (miRBase Accession No. MIMAT0027511 ) and other species homologs or orthologs. The 5-3p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6805-3p has a hairpin-like structure as its precursor, hsa-mir -6805" (miRBase Accession No. MI0022650, sequence Number 324) is known.
[0180] As used herein, "hsa-miR-6808-5p gene" or "hsa-mi The term "miR-6808-5p" refers to hsa-miR-6808 as set forth in SEQ ID NO: 102. -5p gene (miRBase Accession No. MIMAT0027516 ) and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6808-5p has a hairpin-like structure as its precursor, hsa-mir -6808" (miRBase Accession No. MI0022653, sequence Number 325) is known.
[0181] As used herein, "hsa-miR-4449 gene" or "hsa-miR-4 The term "miR-4449" refers to the hsa-miR-4449 gene (miR-4449) set forth in SEQ ID NO: 103. RBase Accession No. MIMAT0018968) and other species The hsa-miR-4449 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4449" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4449" (miRBase Accession No. on No. MI0016792, SEQ ID NO: 326) is known.
[0182] As used herein, "hsa-miR-1199-5p gene" or "hsa-mi The term "miR-1199-5p" refers to hsa-miR-1199 as set forth in SEQ ID NO: 104. -5p gene (miRBase Accession No. MIMAT0031119 ) and other species homologs or orthologs. The 9-5p gene is Salvi A et al., 2013, Int J Oncol, vol. 42, The miR gene can be obtained by the method described on pages 391-402. -1199-5p is a precursor of hsa-mir-11, which has a hairpin-like structure. 99" (miRBase Accession No. MI0020340, SEQ ID NO: 3 27) is known.
[0183] As used herein, "hsa-miR-1275 gene" or "hsa-miR-1 The term "miR-1275" refers to the hsa-miR-1275 gene (miR-1275) set forth in SEQ ID NO: 105. RBase Accession No. MIMAT0005929) and other species The hsa-miR-1275 gene is a member of the Mor In RD et al., 2008, Genome Res, Vol. 18, p. 610-621 hsa-miR-1275 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-1275" ( Session No. MI0006415, SEQ ID NO: 328) is known.
[0184] As used herein, "hsa-miR-4792 gene" or "hsa-miR-4 The term "miR-4792" refers to the hsa-miR-4792 gene (miR-4792) set forth in SEQ ID NO: 106. RBase Accession No. MIMAT0019964) and other species The hsa-miR-4792 gene is a homologue or ortholog of the Per sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4792" can be obtained by the method described above. The miRBase Accession No. 100116666444, which has a hairpin-like structure, is a nucleotide sequence of "hsa-mir-4792" (miRBase Accession No. 1001166664444). The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0017439, sequence number 329.
[0185] As used herein, "hsa-miR-4443 gene" or "hsa-miR-4 The term "miR-4443" refers to the hsa-miR-4443 gene (miR-4443) set forth in SEQ ID NO: 107. RBase Accession No. MIMAT0018961) and other species The hsa-miR-4443 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4443" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4443" (miRBase Accession No. on No. MI0016786, SEQ ID NO: 330) is known.
[0186] As used herein, "hsa-miR-6891-5p gene" or "hsa-mi The term "miR-6891-5p" refers to hsa-miR-6891 set forth in SEQ ID NO: 108. -5p gene (miRBase Accession No. MIMAT0027682 ) and other species homologs or orthologs. The 1-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6891-5p has a hairpin-like structure as its precursor, hsa-mir -6891" (miRBase Accession No. MI0022738, sequence Number 331) is known.
[0187] As used herein, "hsa-miR-6826-5p gene" or "hsa-mi The term "miR-6826-5p" refers to hsa-miR-6826 set forth in SEQ ID NO: 109. -5p gene (miRBase Accession No. MIMAT0027552 ) and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6826-5p has a hairpin-like structure as its precursor, hsa-mir -6826" (miRBase Accession No. MI0022671, sequence Number 332) is known.
[0188] As used herein, "hsa-miR-6807-5p gene" or "hsa-mi The term "miR-6807-5p" refers to hsa-miR-6807 set forth in SEQ ID NO: 110. -5p gene (miRBase Accession No. MIMAT0027514 ) and other species homologs or orthologs. The 7-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6807-5p has a hairpin-like structure as its precursor, hsa-mir -6807" (miRBase Accession No. MI0022652, sequence Number 333) is known.
[0189] As used herein, "hsa-miR-7150 gene" or "hsa-miR-7 The term "miR-7150" refers to the hsa-miR-7150 gene (miR-7150) set forth in SEQ ID NO: 111. RBase Accession No. MIMAT0028211) and other species The hsa-miR-7150 gene is a homologue or ortholog. As A et al., 2009, Nucleic Acids Res, Vol. 37, p3276- 3287. 0” has a hairpin-like structure as its precursor “hsa-mir-7150” (miR Base Accession No. MI0023610, SEQ ID NO: 334) is known are.
[0190] As used herein, "hsa-miR-4534 gene" or "hsa-miR-4 The term "miR-4534" refers to the hsa-miR-4534 gene (miR-4534) set forth in SEQ ID NO: 112. RBase Accession No. MIMAT0019073) and other species The hsa-miR-4534 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4534" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4534" (miRBase Accession No. on No. MI0016901, SEQ ID NO: 335) is known.
[0191] As used herein, "hsa-miR-4476 gene" or "hsa-miR-4 The term "miR-4476" refers to the hsa-miR-4476 gene (miR-4476) set forth in SEQ ID NO: 113. RBase Accession No. MIMAT0019003) and other species The hsa-miR-4476 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4476" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4476" (miRBase Accession No. on No. MI0016828, SEQ ID NO: 336) is known.
[0192] As used herein, "hsa-miR-4649-5p gene" or "hsa-mi The term "miR-4649-5p" refers to hsa-miR-4649 as set forth in SEQ ID NO: 114. -5p gene (miRBase Accession No. MIMAT0019711 ) and other species homologs or orthologs. The 9-5p gene is described in Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4649-5p is a precursor of hsa-mir-464, which has a hairpin-like structure. 9" (miRBase Accession No. MI0017276, SEQ ID NO: 33 7) is known.
[0193] As used herein, "hsa-miR-4525 gene" or "hsa-miR-4 The term "miR-4525" refers to the hsa-miR-4525 gene (miR-4525) set forth in SEQ ID NO: 115. RBase Accession No. MIMAT0019064) and other species The hsa-miR-4525 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 In addition, "hsa-miR-4525" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4525" (miRBase Accession No. on No. MI0016892, SEQ ID NO: 338) is known.
[0194] As used herein, "hsa-miR-1915-3p gene" or "hsa-mi The term "miR-1915-3p" refers to hsa-miR-1915 as set forth in SEQ ID NO: 116. -3p gene (miRBase Accession No. MIMAT0007892 ) and other species homologs or orthologs. The 5-3p gene is described in Bar M et al., 2008, Stem Cells, Vol. 26, p. 24 The "hsa-miR- 1915-3p is a precursor of hsa-mir-191, which has a hairpin-like structure. 5" (miRBase Accession No. MI0008336, SEQ ID NO: 31 1) is known.
[0195] As used herein, "hsa-miR-4516 gene" or "hsa-miR-4 The term "miR-4516" refers to the hsa-miR-4516 gene (miR-4516) set forth in SEQ ID NO: 117. RBase Accession No. MIMAT0019053) and other species The hsa-miR-4516 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 In addition, "hsa-miR-4516" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4516" (miRBase Accession No. on No. MI0016882, SEQ ID NO: 339) is known.
[0196] As used herein, "hsa-miR-4417 gene" or "hsa-miR-4 The term "miR-4417" refers to the hsa-miR-4417 gene (miR-4417) set forth in SEQ ID NO: 118. RBase Accession No. MIMAT0018929) and other species The hsa-miR-4417 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4417" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4417" (miRBase Accession No. on No. MI0016753, SEQ ID NO: 340) is known.
[0197] As used herein, "hsa-miR-642b-3p gene" or "hsa-mi The term "miR-642b-3p" refers to hsa-miR-642b as set forth in SEQ ID NO: 119. -3p gene (miRBase Accession No. MIMAT0018444 ) and other species homologs or orthologs. The b-3p gene is described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58 The "hsa-miR-642b-3p" can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-642b (miRB)" The enzyme (Accession No. MI0016685, SEQ ID NO: 341) is known There are.
[0198] As used herein, "hsa-miR-3141 gene" or "hsa-miR-3 The term "miR-3141" refers to the hsa-miR-3141 gene (miR-3141) set forth in SEQ ID NO: 120. RBase Accession No. MIMAT0015010) and other species The hsa-miR-3141 gene is a homologue or ortholog of the Sta rk MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3141" can be obtained by The pin-like structure of "hsa-mir-3141" (miRBase Accession No. No. MI0014165, SEQ ID NO: 342) is known.
[0199] As used herein, "hsa-miR-5100 gene" or "hsa-miR-5 The term "miR-5100" refers to the hsa-miR-5100 gene (miR-5100) set forth in SEQ ID NO: 121. RBase Accession No. MIMAT0022259) and other species The hsa-miR-5100 gene is a homologue or ortholog. Don M et al., 2012, Oral Dis, Vol. 18, p. 127-131 hsa-miR-5100 can be obtained by the method described above. The miRBase Accession No. 10002266664, which forms a hairpin-like structure, is sion No. MI0019116, SEQ ID NO: 343) is known.
[0200] As used herein, "hsa-miR-6848-5p gene" or "hsa-mi The term "miR-6848-5p" refers to hsa-miR-6848 as set forth in SEQ ID NO: 122. -5p gene (miRBase Accession No. MIMAT0027596 ) and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6848-5p has a hairpin-like structure as its precursor, hsa-mir -6848" (miRBase Accession No. MI0022694, sequence Number 344) is known.
[0201] As used herein, "hsa-miR-4739 gene" or "hsa-miR-4 The term "miR-4739" refers to the hsa-miR-4739 gene (miR-4739) set forth in SEQ ID NO: 123. RBase Accession No. MIMAT0019868) and other species The hsa-miR-4739 gene is a homologue or ortholog of the Per sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4739" can be obtained by the method described above. The miRBase Accession No. 10062666644, which has a hairpin-like structure, is a target gene of interest. The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0017377, sequence number 345.
[0202] As used herein, "hsa-miR-4459 gene" or "hsa-miR-4 The term "miR-4459" refers to the hsa-miR-4459 gene (miR-4459) set forth in SEQ ID NO: 124. RBase Accession No. MIMAT0018981) and other species The hsa-miR-4459 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4459" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4459" (miRBase Accession No. on No. MI0016805, SEQ ID NO: 346) is known.
[0203] As used herein, "hsa-miR-1237-5p gene" or "hsa-mi The term "miR-1237-5p" refers to hsa-miR-1237 as set forth in SEQ ID NO: 125. -5p gene (miRBase Accession No. MIMAT0022946 ) and other species homologs or orthologs. The 7-5p gene is described in Berezikov E et al., 2007, Mol Cell, vol. 28 It can be obtained by the method described in the "Hsa-mi R-1237-5p is a precursor of hsa-mir-1, which has a hairpin-like structure. 237" (miRBase Accession No. MI0006327, SEQ ID NO: 347) is known.
[0204] As used herein, "hsa-miR-296-3p gene" or "hsa-miR The term "miR-296-3p" refers to hsa-miR-296-3p as set forth in SEQ ID NO: 126. Gene (miRBase Accession No. MIMAT0004679) and This includes homologs or orthologs of other species. Genes: Houbaviy HB et al., 2003, Dev Cell, vol. 5, p. 351 The miR-296 can be obtained by the method described in Ref. 358. The precursor of α-3p is hsa-mir-296 (mi RBase Accession No. MI0000747, sequence number 273) It is being done.
[0205] As used herein, "hsa-miR-4665-3p gene" or "hsa-mi The term "miR-4665-3p" refers to hsa-miR-4665 set forth in SEQ ID NO: 127. -3p gene (miRBase Accession No. MIMAT0019740 ) and other species homologs or orthologs. The 5-3p gene is Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4665-3p is a precursor of hsa-mir-466, which has a hairpin-like structure. 5" (miRBase Accession No. MI0017295, SEQ ID NO: 26 9) is known.
[0206] As used herein, "hsa-miR-6786-5p gene" or "hsa-mi The term "miR-6786-5p" refers to hsa-miR-6786 set forth in SEQ ID NO: 128. -5p gene (miRBase Accession No. MIMAT0027472 ) and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6786-5p has a hairpin-like structure as its precursor, hsa-mir -6786" (miRBase Accession No. MI0022631, sequence Number 348) is known.
[0207] As used herein, "hsa-miR-4258 gene" or "hsa-miR-4 The term "miR-4258" refers to the hsa-miR-4258 gene (miR-4258) set forth in SEQ ID NO: 129. RBase Accession No. MIMAT0016879) and other species The hsa-miR-4258 gene is a homologue or ortholog of Gof f By the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 In addition, "hsa-miR-4258" can be obtained by using hairpin as its precursor. The miRBase Accession No. 1000012666644444 has a phosphodiesterase-like structure, "hsa-mir-4258" (miRBase Accession No. 100001266666444444). No. MI0015857, SEQ ID NO: 349) is known.
[0208] As used herein, "hsa-miR-6510-5p gene" or "hsa-mi The term "miR-6510-5p" refers to hsa-miR-6510 set forth in SEQ ID NO: 130. -5p gene (miRBase Accession No. MIMAT0025476 ) and other species homologs or orthologs. The 0-5p gene is Joyce CE et al., 2011, Hum Mol Genet, 2 0, pp. 4025-4040. a-miR-6510-5p has a hairpin-like structure as its precursor, hsa-m ir-6510” (miRBase Accession No. MI0022222, SEQ ID NO: 350) is known.
[0209] As used herein, "hsa-miR-1343-5p gene" or "hsa-mi The term "miR-1343-5p" refers to hsa-miR-1343 as set forth in SEQ ID NO: 131. -5p gene (miRBase Accession No. MIMAT0027038 ) and other species homologs or orthologs. The 3-5p gene is Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 1343-5p is a precursor of hsa-mir-134, which has a hairpin-like structure. 3" (miRBase Accession No. MI0017320, SEQ ID NO: 22 5) is known.
[0210] As used herein, the term "hsa-miR-1247-3p gene" or "hsa-mi The term "miR-1247-3p" refers to hsa-miR-1247 as set forth in SEQ ID NO: 132. -3p gene (miRBase Accession No. MIMAT0022721 ) and other species homologs or orthologs. The 7-3p gene is described in Morin RD et al., 2008, Genome Res, Vol. 18, The miR gene can be obtained by the method described on pages 610-621. -1247-3p is a precursor of hsa-mir-12, which has a hairpin-like structure. 47" (miRBase Accession No. MI0006382, SEQ ID NO: 3 51) is known.
[0211] As used herein, "hsa-miR-6805-5p gene" or "hsa-mi The term "miR-6805-5p" refers to hsa-miR-6805 as set forth in SEQ ID NO: 133. -5p gene (miRBase Accession No. MIMAT0027510 ) and other species homologs or orthologs. The 5-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6805-5p has a hairpin-like structure as its precursor, hsa-mir -6805" (miRBase Accession No. MI0022650, sequence Number 324) is known.
[0212] As used herein, "hsa-miR-4492 gene" or "hsa-miR-4 The term "miR-4492" refers to the hsa-miR-4492 gene (miR-4492) set forth in SEQ ID NO: 134. RBase Accession No. MIMAT0019027) and other species The hsa-miR-4492 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4492" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4492" (miRBase Accession No. on No. MI0016854, SEQ ID NO: 352) is known.
[0213] As used herein, "hsa-miR-1469 gene" or "hsa-miR-1 The term "miR-1469" refers to the hsa-miR-1469 gene (miR-1469) set forth in SEQ ID NO: 135. RBase Accession No. MIMAT0007347) and other species The hsa-miR-1469 gene is a homologue or ortholog of the Kaw Aji H et al., 2008, BMC Genomics, Vol. 9, p. 157 hsa-miR-1469 can be obtained by the method described above. The miRBase Accession No. 1006266666826 forms a hairpin-like structure. ion No. MI0007074, SEQ ID NO: 353) is known.
[0214] As used herein, "hsa-miR-1268b gene" or "hsa-miR- The term "miR-1268b" refers to the hsa-miR-1268b gene set forth in SEQ ID NO: 136. (miRBase Accession No. MIMAT0018925) and other The hsa-miR-1268b gene includes species homologs or orthologs. , Jima DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-1268b can be obtained by the method described above. The miRBase A receptor has a hairpin-like structure as a carrier. Accession No. MI0016748, SEQ ID NO: 354) is known.
[0215] As used herein, "hsa-miR-6858-5p gene" or "hsa-mi The term "miR-6858-5p" refers to hsa-miR-6858 as set forth in SEQ ID NO: 137. -5p gene (miRBase Accession No. MIMAT0027616 ) and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6858-5p has a hairpin-like structure as its precursor, hsa-mir -6858" (miRBase Accession No. MI0022704, sequence Number 355) is known.
[0216] As used herein, "hsa-miR-3937 gene" or "hsa-miR-3 The term "miR-3937" refers to the hsa-miR-3937 gene (miR-3937) set forth in SEQ ID NO: 138. RBase Accession No. MIMAT0018352) and other species The hsa-miR-3937 gene is a homologue or ortholog of the Lia o JY et al., 2010, PLoS One, Vol. 5, e10563 In addition, "hsa-miR-3937" can be obtained by The pin-like structure of "hsa-mir-3937" (miRBase Accession No. No. MI0016593, SEQ ID NO: 356) is known.
[0217] As used herein, "hsa-miR-939-5p gene" or "hsa-miR The term "miR-939-5p" refers to hsa-miR-939-5p set forth in SEQ ID NO: 139. Gene (miRBase Accession No. MIMAT0004982) and This includes homologs or orthologs of other species. The gene is described in Lui WO et al., 2007, Cancer Res, Vol. 67, p6031- The miR-939 can be obtained by the method described in 6043. -5p" has a hairpin-like structure as its precursor, "hsa-mir-939" (mi RBase Accession No. MI0005761, sequence number 357) It is being done.
[0218] As used herein, "hsa-miR-3656 gene" or "hsa-miR-3 The term "miR-3656" refers to the hsa-miR-3656 gene (miR-3656) set forth in SEQ ID NO: 140. RBase Accession No. MIMAT0018076) and other species The hsa-miR-3656 gene includes homologs or orthologs. ri E et al., 2010, Nucleic Acids Res, Vol. 38, p6234- The miR-365 gene can be obtained by the method described in 6246. 6” has a hairpin-like structure as its precursor, “hsa-mir-3656” (miR Base Accession No. MI0016056, SEQ ID NO: 358) is known are.
[0219] As used herein, "hsa-miR-744-5p gene" or "hsa-miR The term "miR-744-5p" refers to hsa-miR-744-5p as set forth in SEQ ID NO: 141. Gene (miRBase Accession No. MIMAT0004945) and This includes homologs or orthologs of hsa-miR-744-5p from other species. Genes: Berezikov E et al., 2006, Genome Res, vol. 16, p. It can be obtained by the method described in 1289-1298. R-744-5p has a hairpin-like structure as its precursor, hsa-mir-74 4" (miRBase Accession No. MI0005559, SEQ ID NO: 35 9) is known.
[0220] As used herein, "hsa-miR-4687-3p gene" or "hsa-mi The term "miR-4687-3p" refers to hsa-miR-4687 as set forth in SEQ ID NO: 142. -3p gene (miRBase Accession No. MIMAT0019775 ) and other species homologs or orthologs. The 7-3p gene is described in Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4687-3p is a precursor of hsa-mir-468, which has a hairpin-like structure. 7" (miRBase Accession No. MI0017319, SEQ ID NO: 36 0) is known.
[0221] As used herein, "hsa-miR-4763-3p gene" or "hsa-mi The term "miR-4763-3p" refers to hsa-miR-4763 as set forth in SEQ ID NO: 143. -3p gene (miRBase Accession No. MIMAT0019913 ) and other species homologs or orthologs. The 3-3p gene is described in Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4763-3p is a precursor of hsa-mir-476, which has a hairpin-like structure. 3" (miRBase Accession No. MI0017404, SEQ ID NO: 36 1) is known.
[0222] As used herein, "hsa-miR-3620-5p gene" or "hsa-mi The term "miR-3620-5p" refers to hsa-miR-3620 set forth in SEQ ID NO: 144. -5p gene (miRBase Accession No. MIMAT0022967 ) and other species homologs or orthologs. The 0-5p gene is described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58 The miR-3620-5p gene can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-3620" (miRB The enzyme (Accession No. MI0016011, SEQ ID NO: 362) is known There are.
[0223] As used herein, "hsa-miR-3195 gene" or "hsa-miR-3 The term "miR-3195" refers to the hsa-miR-3195 gene (miR-3195) set forth in SEQ ID NO: 145. RBase Accession No. MIMAT0015079) and other species The hsa-miR-3195 gene is a homologue or ortholog of the Sta rk MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3195" can be obtained by The pin-like structure of "hsa-mir-3195" (miRBase Accession No. No. MI0014240, SEQ ID NO: 363) is known.
[0224] As used herein, "hsa-miR-6842-5p gene" or "hsa-mi The term "miR-6842-5p" refers to hsa-miR-6842 as set forth in SEQ ID NO: 146. -5p gene (miRBase Accession No. MIMAT0027586 ) and other species homologs or orthologs. The 2-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6842-5p has a hairpin-like structure as its precursor, hsa-mir -6842" (miRBase Accession No. MI0022688, sequence Number 364) is known.
[0225] As used herein, "hsa-miR-4707-5p gene" or "hsa-mi The term "miR-4707-5p" refers to hsa-miR-4707 set forth in SEQ ID NO: 147. -5p gene (miRBase Accession No. MIMAT0019807 ) and other species homologs or orthologs. The 7-5p gene is described in Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4707-5p is a precursor of hsa-mir-470, which has a hairpin-like structure. 7" (miRBase Accession No. MI0017340, SEQ ID NO: 36 5) is known.
[0226] As used herein, "hsa-miR-642a-3p gene" or "hsa-mi The term "miR-642a-3p" refers to hsa-miR-642a set forth in SEQ ID NO: 148. -3p gene (miRBase Accession No. MIMAT0020924 ) and other species homologs or orthologs. The a-3p gene is described in Cummins JM et al., 2006, Proc Natl Aca d Sci USA, Vol. 103, pp. 3687-3692. In addition, "hsa-miR-642a-3p" is a precursor of hair follicles. The pin-like structure of "hsa-mir-642a" (miRBase Accession No. No. MI0003657, SEQ ID NO: 366) is known.
[0227] As used herein, "hsa-miR-7113-3p gene" or "hsa-mi The term "miR-7113-3p" refers to hsa-miR-7113 as set forth in SEQ ID NO: 149. -3p gene (miRBase Accession No. MIMAT0028124 ) and other species homologs or orthologs. The 3-3p gene is described in Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-7113-3p has a hairpin-like structure as its precursor, hsa-mir -7113" (miRBase Accession No. MI0022964, sequence Number 367) is known.
[0228] As used herein, "hsa-miR-4728-5p gene" or "hsa-mi The term "miR-4728-5p" refers to hsa-miR-4728 as set forth in SEQ ID NO: 150. -5p gene (miRBase Accession No. MIMAT0019849 ) and other species homologs or orthologs. The 8-5p gene is Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4728-5p is a precursor of hsa-mir-472, which has a hairpin-like structure. 8" (miRBase Accession No. MI0017365, SEQ ID NO: 36 8) is known.
[0229] As used herein, "hsa-miR-5195-3p gene" or "hsa-mi The term "miR-5195-3p" refers to hsa-miR-5195 as set forth in SEQ ID NO: 151. -3p gene (miRBase Accession No. MIMAT0021127 ) and other species homologs or orthologs. The 5-3p gene is described in Schotte D et al., 2011, Leukemia, Vol. 25, p. It can be obtained by the method described in 1389-1399. R-5195-3p is a precursor of hsa-mir-5, which has a hairpin-like structure. 195" (miRBase Accession No. MI0018174, SEQ ID NO: 369) is known.
[0230] As used herein, "hsa-miR-1185-1-3p gene" or "hsa- The term "miR-1185-1-3p" refers to the hsa-miR- 1185-1-3p gene (miRBase Accession No. MIMAT0 022838) and other species homologs or orthologs. The iR-1185-1-3p gene was identified in Berezikov E et al., 2006, Geno It can be obtained by the method described in Me Res, Vol. 16, pp. 1289-1298. In addition, "hsa-miR-1185-1-3p" has a hairpin-like structure as its precursor. The structure of "hsa-mir-1185-1" (miRBase Accession No. o.MI0003844, SEQ ID NO: 370) is known.
[0231] As used herein, "hsa-miR-6774-5p gene" or "hsa-mi The term "miR-6774-5p" refers to hsa-miR-6774 set forth in SEQ ID NO: 153. -5p gene (miRBase Accession No. MIMAT0027448 ) and other species homologs or orthologs. The 4-5p genes are described in Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6774-5p has a hairpin-like structure as its precursor, hsa-mir -6774" (miRBase Accession No. MI0022619, sequence Number 371) is known.
[0232] As used herein, "hsa-miR-8059 gene" or "hsa-miR-8 The term "miR-8059" refers to the hsa-miR-8059 gene (miR-8059) set forth in SEQ ID NO: 154. RBase Accession No. MIMAT0030986) and other species The hsa-miR-8059 gene is a homologue or ortholog. g HJ et al., 2013, Shock, Vol. 39, p. 480-487 In addition, "hsa-miR-8059" can be obtained by The pin-like structure of "hsa-mir-8059" (miRBase Accession No. No. MI0025895, SEQ ID NO: 372) is known.
[0233] As used herein, "hsa-miR-3131 gene" or "hsa-miR-3 The term "miR-3131" refers to the hsa-miR-3131 gene (miR-3131) set forth in SEQ ID NO: 155. RBase Accession No. MIMAT0014996) and other species The hsa-miR-3131 gene is a homologue or ortholog of the Sta rk MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3131" can be obtained by The pin-like structure of "hsa-mir-3131" (miRBase Accession No. No. MI0014151, SEQ ID NO: 373) is known.
[0234] As used herein, "hsa-miR-7847-3p gene" or "hsa-mi The term "miR-7847-3p" refers to hsa-miR-7847 as set forth in SEQ ID NO: 156. -3p gene (miRBase Accession No. MIMAT0030422 ) and other species homologs or orthologs. The 7-3p gene is Ple H et al., 2012, PLoS One, Vol. 7, e50746 The miR-7847-3p gene can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-7847" (miRB The enzyme (Accession No. MI0025517, SEQ ID NO: 374) is known There are.
[0235] As used herein, "hsa-miR-4463 gene" or "hsa-miR-4 The term "miR-4463" refers to the hsa-miR-4463 gene (miR-4463) set forth in SEQ ID NO: 157. RBase Accession No. MIMAT0018987) and other species The hsa-miR-4463 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4463" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4463" (miRBase Accession No. on No. MI0016811, SEQ ID NO: 375) is known.
[0236] As used herein, "hsa-miR-128-2-5p gene" or "hsa-m The term "miR-128-2-5p" refers to hsa-miR-128-2-5p as set forth in SEQ ID NO: 158. 8-2-5p gene (miRBase Accession No. MIMAT0031 095) and other species homologs or orthologs. The 128-2-5p gene is Lagos-Quintana M et al., 2002, Cur It can be obtained by the method described in rBiol, vol. 12, pp. 735-739. In addition, "hsa-miR-128-2-5p" has a hairpin-like structure as its precursor. "hsa-mir-128-2" (miRBase Accession No. MI 0000727, SEQ ID NO: 376) is known.
[0237] As used herein, "hsa-miR-4508 gene" or "hsa-miR-4 The term "miR-4508" refers to the hsa-miR-4508 gene (miR-4508) set forth in SEQ ID NO: 159. RBase Accession No. MIMAT0019045) and other species The hsa-miR-4508 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4508" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4508" (miRBase Accession No. on No. MI0016872, SEQ ID NO: 377) is known.
[0238] As used herein, "hsa-miR-6806-5p gene" or "hsa-mi The term "miR-6806-5p" refers to hsa-miR-6806 set forth in SEQ ID NO: 160. -5p gene (miRBase Accession No. MIMAT0027512 ) and other species homologs or orthologs. The 6-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6806-5p has a hairpin-like structure as its precursor, hsa-mir -6806" (miRBase Accession No. MI0022651, sequence Number 378) is known.
[0239] As used herein, "hsa-miR-7111-5p gene" or "hsa-mi The term "miR-7111-5p" refers to hsa-miR-7111 set forth in SEQ ID NO: 161. -5p gene (miRBase Accession No. MIMAT0028119 ) and other species homologs or orthologs. The 1-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-7111-5p has a hairpin-like structure as its precursor, hsa-mir -7111" (miRBase Accession No. MI0022962, sequence Number 379) is known.
[0240] As used herein, "hsa-miR-6782-5p gene" or "hsa-mi The term "miR-6782-5p" refers to hsa-miR-6782 set forth in SEQ ID NO: 162. -5p gene (miRBase Accession No. MIMAT0027464 ) and other species homologs or orthologs. The 2-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6782-5p has a hairpin-like structure as its precursor, hsa-mir -6782" (miRBase Accession No. MI0022627, sequence Number 380) is known.
[0241] As used herein, "hsa-miR-4734 gene" or "hsa-miR-4 The term "miR-4734" refers to the hsa-miR-4734 gene (miR-4734) set forth in SEQ ID NO: 163. RBase Accession No. MIMAT0019859) and other species The hsa-miR-4734 gene is a homologue or ortholog of the Per sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4734" can be obtained by the method described above. The miRBase Accession No. 1000012666666, which has a hairpin-like structure, is a nucleotide sequence of the miR-1 gene. The sequence number of the gene encoding the nucleotide sequence of the present invention is 381 (sequence number MI0017371, sequence number 381).
[0242] As used herein, "hsa-miR-3162-5p gene" or "hsa-mi The term "miR-3162-5p" refers to hsa-miR-3162 set forth in SEQ ID NO: 164. -5p gene (miRBase Accession No. MIMAT0015036 ) and other species homologs or orthologs. The 2-5p gene is Stark MS et al., 2010, PLoS One, Vol. 5, e96 The miR-3162 gene can be obtained by the method described in 85. 5p" has a hairpin-like structure as its precursor "hsa-mir-3162" (mi RBase Accession No. MI0014192, sequence number 382) is known. It is being done.
[0243] As used herein, "hsa-miR-887-3p gene" or "hsa-miR The term "miR-887-3p" refers to hsa-miR-887-3p set forth in SEQ ID NO: 165. Gene (miRBase Accession No. MIMAT0004951) and This includes homologs or orthologs of other species. Genes: Berezikov E et al., 2006, Genome Res, vol. 16, p. It can be obtained by the method described in 1289-1298. R-887-3p is a precursor of hsa-mir-88, which has a hairpin-like structure. 7" (miRBase Accession No. MI0005562, SEQ ID NO: 38 3) is known.
[0244] As used herein, "hsa-miR-6752-5p gene" or "hsa-mi The term "miR-6752-5p" refers to hsa-miR-6752 as set forth in SEQ ID NO: 166. -5p gene (miRBase Accession No. MIMAT0027404 ) and other species homologs or orthologs. The 2-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6752-5p has a hairpin-like structure as its precursor, hsa-mir -6752" (miRBase Accession No. MI0022597, sequence Number 384) is known.
[0245] As used herein, "hsa-miR-6724-5p gene" or "hsa-mi The term "miR-6724-5p" refers to hsa-miR-6724 set forth in SEQ ID NO: 167. -5p gene (miRBase Accession No. MIMAT0025856 ) and other species homologs or orthologs. The 4-5p gene is described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. It can be obtained by the method described in the specification. The precursor of miRBa is “hsa-mir-6724” (miRBa (Accession No. MI0022559, SEQ ID NO: 385) do.
[0246] As used herein, "hsa-miR-23b-3p gene" or "hsa-miR The term "miR-23b-3p" refers to hsa-miR-23b-3p set forth in SEQ ID NO: 168. Gene (miRBase Accession No. MIMAT0000418) and This includes homologs or orthologs of hsa-miR-23b-3p from other species. The gene is from Lagos-Quintana M et al., 2002, Curr Biol, 1 It can be obtained by the method described in Vol. 2, pp. 735-739. miR-23b-3p has a hairpin-like structure as its precursor, hsa-mir- 23b" (miRBase Accession No. MI0000439, SEQ ID NO: 386) is known.
[0247] As used herein, "hsa-miR-23a-3p gene" or "hsa-miR The term "miR-23a-3p" refers to hsa-miR-23a-3p as set forth in SEQ ID NO: 169. Gene (miRBase Accession No. MIMAT0000078) and This includes homologs or orthologs of hsa-miR-23a-3p from other species. Genes: Lagos-Quintana M et al., 2001, Science, 294 It can be obtained by the method described in Vol. 1, pp. 853-858. iR-23a-3p is a precursor of hsa-mir-2, which has a hairpin-like structure. 3a" (miRBase Accession No. MI0000079, SEQ ID NO: 3 87) is known.
[0248] As used herein, "hsa-miR-625-3p gene" or "hsa-miR The term "miR-625-3p" refers to hsa-miR-625-3p as set forth in SEQ ID NO: 170. Gene (miRBase Accession No. MIMAT0004808) and This includes homologs or orthologs of other species. Genes are listed in Cummins JM et al., 2006, Proc Natl Acad Sc i Obtained by the method described in USA, Vol. 103, pp. 3687-3692 In addition, "hsa-miR-625-3p" has a hairpin-like structure as its precursor. The miRBase Accession No. I0003639, SEQ ID NO: 388) is known.
[0249] As used herein, "hsa-miR-1228-3p gene" or "hsa-mi The term "miR-1228-3p" refers to hsa-miR-1228 as set forth in SEQ ID NO: 171. -3p gene (miRBase Accession No. MIMAT0005583 ) and other species homologs or orthologs. The 8-3p gene is described in Berezikov E et al., 2007, Mol Cell, vol. 28 It can be obtained by the method described in the "Hsa-mi R-1228-3p is a precursor of hsa-mir-1, which has a hairpin-like structure. 228" (miRBase Accession No. MI0006318, SEQ ID NO: 316) is known.
[0250] As used herein, "hsa-miR-614 gene" or "hsa-miR-61 The term "miR-614" refers to the hsa-miR-614 gene (miRBa se Accession No. MIMAT0003282) and other species homologs The hsa-miR-614 gene is also included in the Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103 It can be obtained by the method described in the "hsa- miR-614 has a hairpin-like structure as its precursor, hsa-mir-614 ” (miRBase Accession No. MI0003627, SEQ ID NO: 389 ) is known.
[0251] As used herein, "hsa-miR-1913 gene" or "hsa-miR-1 The term "miR-1913" refers to the hsa-miR-1913 gene (miR-1913) set forth in SEQ ID NO: 173. RBase Accession No. MIMAT0007888) and other species The hsa-miR-1913 gene is a homologue or ortholog of the Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505 Furthermore, "hsa-miR-1913" can be obtained by the method described above. The miRBase Accession No. 1344444 (hsa-mir-1913) has a hairpin-like structure as a The sequence number of the nucleotide sequence ...
[0252] As used herein, "hsa-miR-92a-2-5p gene" or "hsa-m The term "miR-92a-2-5p" refers to hsa-miR-92a-2-5p as set forth in SEQ ID NO: 174. a-2-5p gene (miRBase Accession No. MIMAT0004 508) and other species homologs or orthologs. The 92a-2-5p gene is described in Mourelatos Z et al., 2002, Genes D EV, Vol. 16, pp. 720-728. hsa-miR-92a-2-5p is a precursor of hs a-mir-92a-2” (miRBase Accession No. MI0000 094, SEQ ID NO: 391) is known.
[0253] As used herein, "hsa-miR-187-5p gene" or "hsa-miR The term "miR-187-5p" refers to hsa-miR-187-5p as set forth in SEQ ID NO: 175. Gene (miRBase Accession No. MIMAT0004561) and This includes homologs or orthologs of other species. The gene is described in Lim LP et al., 2003, Science, Vol. 299, p. 1540. Furthermore, "hsa-miR-187-5p" can be obtained by the method described above. The precursor of the hairpin-like structure "hsa-mir-187" (miRBase A Accession No. MI0000274, SEQ ID NO: 392) is known.
[0254] As used herein, "hsa-miR-16-5p gene" or "hsa-miR- The term "miR-16-5p" refers to the hsa-miR-16-5p gene set forth in SEQ ID NO: 176. (miRBase Accession No. MIMAT0000069) and other The hsa-miR-16-5p gene includes species homologs or orthologs. , Lagos-Quintana M et al., 2001, Science, Vol. 294, p. 8 53-858. 6-5p" has a hairpin-like structure as its precursor, "hsa-mir-16-1", "hsa-mir-16-2" (miRBase Accession No. MI00 00070, MI0000115, SEQ ID NOs: 393, 394) are known.
[0255] As used herein, "hsa-miR-92b-3p gene" or "hsa-miR The term "miR-92b-3p" refers to hsa-miR-92b-3p set forth in SEQ ID NO: 177. Gene (miRBase Accession No. MIMAT0003218) and This includes homologs or orthologs of hsa-miR-92b-3p from other species. Genes are listed in Cummins JM et al., 2006, Proc Natl Acad Sc i USA, Vol. 103, pp. 3687-3692 In addition, "hsa-miR-92b-3p" has a hairpin-like structure as its precursor. The miRBase Accession No. 0003560, SEQ ID NO: 395) is known.
[0256] As used herein, "hsa-miR-150-3p gene" or "hsa-miR The term "miR-150-3p" refers to hsa-miR-150-3p set forth in SEQ ID NO: 178. Gene (miRBase Accession No. MIMAT0004610) and This includes homologs or orthologs of other species. The gene is from Lagos-Quintana M et al., 2002, Curr Biol, 1 It can be obtained by the method described in Vol. 2, pp. 735-739. miR-150-3p has a hairpin-like structure as its precursor, hsa-mir- 150" (miRBase Accession No. MI0000479, SEQ ID NO: 396) is known.
[0257] As used herein, "hsa-miR-564 gene" or "hsa-miR-56 The term "miR-564" refers to the hsa-miR-564 gene (miRBa se Accession No. MIMAT0003228) and other species homologs The hsa-miR-564 gene is a member of the Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103 It can be obtained by the method described in the "hsa- miR-564 has a hairpin-like structure as its precursor, hsa-mir-564 ” (miRBase Accession No. MI0003570, SEQ ID NO: 397 ) is known.
[0258] As used herein, "hsa-miR-125a-3p gene" or "hsa-mi The term "miR-125a-3p" refers to hsa-miR-125a as set forth in SEQ ID NO: 180. -3p gene (miRBase Accession No. MIMAT0004602 ) and other species homologs or orthologs. The a-3p gene is described in Lagos-Quintana M et al., 2002, Curr Biology It can be obtained by the method described in Vol. 12, pp. 735-739. hsa-miR-125a-3p is a precursor of hsa -mir-125a” (miRBase Accession No. MI000046 9, SEQ ID NO: 398) is known.
[0259] As used herein, "hsa-miR-92b-5p gene" or "hsa-miR The term "miR-92b-5p" refers to hsa-miR-92b-5p as set forth in SEQ ID NO: 181. Gene (miRBase Accession No. MIMAT0004792) and This includes homologs or orthologs of hsa-miR-92b-5p from other species. Genes are listed in Cummins JM et al., 2006, Proc Natl Acad Sc i USA, Vol. 103, pp. 3687-3692 In addition, "hsa-miR-92b-5p" has a hairpin-like structure as its precursor. The miRBase Accession No. 0003560, SEQ ID NO: 395) is known.
[0260] As used herein, "hsa-miR-92a-3p gene" or "hsa-miR The term "miR-92a-3p" refers to hsa-miR-92a-3p as set forth in SEQ ID NO: 182. Gene (miRBase Accession No. MIMAT0000092) and This includes homologs or orthologs of hsa-miR-92a-3p from other species. Genes: Mourelatos Z et al., 2002, Genes Dev, vol. 16, p. The "hsa-miR- The precursor of 92a-3p is a hairpin-like structure called hsa-mir-92a- 1”, “hsa-mir-92a-2” (miRBase Accession No. MI0000093, MI0000094, SEQ ID NOs: 399, 391) are known.
[0261] As used herein, "hsa-miR-663a gene" or "hsa-miR-6 The term "miR-663a" refers to the hsa-miR-663a gene (mi RBase Accession No. MIMAT0003326) and other species The hsa-miR-663a gene is a homologue or ortholog of the Cum mins JM et al., 2006, Proc Natl Acad Sci USA, It can be obtained by the method described in Vol. 103, pp. 3687-3692. hsa-miR-663a is a precursor of hsa-miR, which has a hairpin-like structure. r-663a” (miRBase Accession No. MI0003672, Column number 400) is known.
[0262] As used herein, "hsa-miR-4688 gene" or "hsa-miR-4 The term "miR-4688" refers to the hsa-miR-4688 gene (miR-4688) set forth in SEQ ID NO: 184. RBase Accession No. MIMAT0019777) and other species The hsa-miR-4688 gene is a homologue or ortholog of the Per sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4688" can be obtained by the method described above. The miRBase Accession No. 100002666666666688 has a hairpin-like structure as a target protein. The sequence number of the nucleotide sequence ...
[0263] As used herein, "hsa-miR-4648 gene" or "hsa-miR-4 The term "miR-4648" refers to the hsa-miR-4648 gene (miR-4648) set forth in SEQ ID NO: 185. RBase Accession No. MIMAT0019710) and other species The hsa-miR-4648 gene is a homologue or ortholog. sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4648" can be obtained by the method described above. The miRBase Accession No. 1000026666668 has a hairpin-like structure as a target gene. The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0017275, sequence number 402.
[0264] As used herein, "hsa-miR-6085 gene" or "hsa-miR-6 The term "miR-6085" refers to the hsa-miR-6085 gene (miR-6085) set forth in SEQ ID NO: 186. RBase Accession No. MIMAT0023710) and other species The hsa-miR-6085 gene is a homologue or ortholog of the Voe The method described in Illenkle C et al., 2012, RNA, Vol. 18, p. 472-484 hsa-miR-6085 can be obtained by the method described above. The miRBase Accession No. 100002666666 (hsa-mir-6085) (miRBase Accession No. 1000026666666) forms a hairpin-like structure. ion No. MI0020362, SEQ ID NO: 403) is known.
[0265] As used herein, "hsa-miR-6126 gene" or "hsa-miR-6 The term "miR-6126" refers to the hsa-miR-6126 gene (miR-6126) set forth in SEQ ID NO: 187. RBase Accession No. MIMAT0024599) and other species The hsa-miR-6126 gene is a homologue or ortholog of the Smi th JL et al., 2012, J Virol, Vol. 86, p5278-5287 Furthermore, "hsa-miR-6126" can be obtained by the method described above. The miRBase Accession No. 10000126 (hsa-mir-6126) has a hairpin-like structure as a The sequence number of the nucleotide sequence ...
[0266] As used herein, "hsa-miR-6880-5p gene" or "hsa-mi The term "miR-6880-5p" refers to hsa-miR-6880 set forth in SEQ ID NO: 188. -5p gene (miRBase Accession No. MIMAT0027660 ) and other species homologs or orthologs. The 0-5p gene is Ladewig E et al., 2012, Genome Res, vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6880-5p has a hairpin-like structure as its precursor, hsa-mir -6880" (miRBase Accession No. MI0022727, sequence Number 405) is known.
[0267] As used herein, "hsa-miR-328-5p gene" or "hsa-miR The term "miR-328-5p" refers to hsa-miR-328-5p set forth in SEQ ID NO: 189. Gene (miRBase Accession No. MIMAT0026486) and This includes homologs or orthologs of other species. Genes are listed in Kim J et al., 2004, Proc Natl Acad Sci US A, Vol. 101, pp. 360-365. "hsa-miR-328-5p" is a precursor of "hsa" which has a hairpin-like structure. -mir-328” (miRBase Accession No. MI0000804 , SEQ ID NO: 406) is known.
[0268] As used herein, "hsa-miR-6768-5p gene" or "hsa-mi The term "miR-6768-5p" refers to hsa-miR-6768 set forth in SEQ ID NO: 190. -5p gene (miRBase Accession No. MIMAT0027436 ) and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6768-5p has a hairpin-like structure as its precursor, hsa-mir -6768" (miRBase Accession No. MI0022613, sequence Number 407) is known.
[0269] As used herein, "hsa-miR-3180 gene" or "hsa-miR-3 The term "miR-3180" refers to the hsa-miR-3180 gene (miR-3180) set forth in SEQ ID NO: 191. RBase Accession No. MIMAT0018178) and other species The hsa-miR-3180 gene is expressed by Cre Lighton CJ et al., 2010, PLoS One, vol. 5, e9637 hsa-miR-3180 can be obtained by the method described above. The hairpin-like structures of "hsa-mir-3180-4" and "hsa-mir-31" are 80-5” (miRBase Accession No. MI0016408, MI0 016409, SEQ ID NOs: 408, 409) are known.
[0270] As used herein, "hsa-miR-6087 gene" or "hsa-miR-6 The term "miR-6087" refers to the hsa-miR-6087 gene (miR-6087) set forth in SEQ ID NO: 192. RBase Accession No. MIMAT0023712) and other species The hsa-miR-6087 gene is a homologue or ortholog of the Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057 Furthermore, "hsa-miR-6087" can be obtained by the method described in Its precursor, "hsa-mir-6087" (miRBase Accession No. MI0020364, SEQ ID NO: 410) is known.
[0271] As used herein, "hsa-miR-1273g-3p gene" or "hsa-m The term "miR-1273g-3p" refers to hsa-miR-12 73g-3p gene (miRBase Accession No. MIMAT0022 742) and other species homologs or orthologs. The 1273g-3p gene is described in Reshmi G et al., 2011, Genomics, 97 It can be obtained by the method described in Vol. 1, pp. 333-340. iR-1273g-3p is a precursor of hsa-mir, which has a hairpin-like structure. -1273g” (miRBase Accession No. MI0018003, Column number 411) is known.
[0272] As used herein, "hsa-miR-1225-5p gene" or "hsa-mi The term "miR-1225-5p" refers to hsa-miR-1225 as set forth in SEQ ID NO: 194. -5p gene (miRBase Accession No. MIMAT0005572 ) and other species homologs or orthologs. The 5-5p gene is described in Berezikov E et al., 2007, Mol Cell, vol. 28 It can be obtained by the method described in the "Hsa-mi R-1225-5p is a precursor of hsa-mir-1, which has a hairpin-like structure. 225" (miRBase Accession No. MI0006311, SEQ ID NO: 303) is known.
[0273] As used herein, "hsa-miR-3196 gene" or "hsa-miR-3 The term "miR-3196" refers to the hsa-miR-3196 gene (miR-3196) set forth in SEQ ID NO: 195. RBase Accession No. MIMAT0015080) and other species The hsa-miR-3196 gene is a homologue or ortholog of the Sta rk MS et al., 2010, PLoS One, Vol. 5, e9685 In addition, "hsa-miR-3196" can be obtained by The pin-like structure of "hsa-mir-3196" (miRBase Accession No. No. MI0014241, SEQ ID NO: 412) is known.
[0274] As used herein, "hsa-miR-4695-5p gene" or "hsa-mi The term "miR-4695-5p" refers to hsa-miR-4695 as set forth in SEQ ID NO: 196. -5p gene (miRBase Accession No. MIMAT0019788 ) and other species homologs or orthologs. The 5-5p gene is described in Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4695-5p is a precursor of hsa-mir-469, which has a hairpin-like structure. 5" (miRBase Accession No. MI0017328, SEQ ID NO: 41 3) is known.
[0275] As used herein, "hsa-miR-6732-5p gene" or "hsa-mi The term "miR-6732-5p" refers to hsa-miR-6732 set forth in SEQ ID NO: 197. -5p gene (miRBase Accession No. MIMAT0027365 ) and other species homologs or orthologs. The 2-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6732-5p has a hairpin-like structure as its precursor, hsa-mir -6732" (miRBase Accession No. MI0022577, sequence Number 414) is known.
[0276] As used herein, "hsa-miR-638 gene" or "hsa-miR-63 The term "miR-638" refers to the hsa-miR-638 gene (miRBa se Accession No. MIMAT0003308) and other species homologs The hsa-miR-638 gene is a member of the Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103 It can be obtained by the method described in the "hsa- miR-638 has a hairpin-like structure as its precursor, hsa-mir-638 ” (miRBase Accession No. MI0003653, SEQ ID NO: 415 ) is known.
[0277] As used herein, "hsa-miR-6813-5p gene" or "hsa-mi The term "miR-6813-5p" refers to hsa-miR-6813 as set forth in SEQ ID NO: 199. -5p gene (miRBase Accession No. MIMAT0027526 ) and other species homologs or orthologs. The 3-5p genes are described in Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6813-5p has a hairpin-like structure as its precursor, hsa-mir -6813" (miRBase Accession No. MI0022658, sequence Number 416) is known.
[0278] As used herein, "hsa-miR-665 gene" or "hsa-miR-66 The term "miR-665" refers to the hsa-miR-665 gene (miRBa se Accession No. MIMAT0004952) and other species homologs or orthologues thereof. ov E et al., 2006, Genome Res, vol. 16, pp. 1289-1298 Furthermore, "hsa-miR-665" can be obtained by the method described above. The miRBase Accession No. 10000126665 (hsa-mir-665) has a hairpin-like structure as a target. The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0005563, sequence number 417.
[0279] As used herein, "hsa-miR-486-3p gene" or "hsa-miR The term "miR-486-3p" refers to hsa-miR-486-3p as set forth in SEQ ID NO: 201. Gene (miRBase Accession No. MIMAT0004762) and This includes homologs or orthologs of other species. Genes: Fu H et al., 2005, FEBS Lett, vol. 579, p3849-38 54. Also, "hsa-miR-486-3 p" has a hairpin-like structure as its precursor, "hsa-mir-486" and "hsa -mir-486-2” (miRBase Accession No. MI00024 70, MI0023622, SEQ ID NOs: 418, 419) are known.
[0280] As used herein, "hsa-miR-4466 gene" or "hsa-miR-4 The term "miR-4466" refers to the hsa-miR-4466 gene (miR-4466) set forth in SEQ ID NO: 202. RBase Accession No. MIMAT0018993) and other species The hsa-miR-4466 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 In addition, "hsa-miR-4466" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4466" (miRBase Accession No. on No. MI0016817, SEQ ID NO: 420) is known.
[0281] As used herein, "hsa-miR-30c-1-3p gene" or "hsa-m The term "miR-30c-1-3p" refers to hsa-miR-30c-1-3p as set forth in SEQ ID NO: 203. c-1-3p gene (miRBase Accession No. MIMAT0004 674) and other species homologs or orthologs. The 30c-1-3p gene is described in Lagos-Quintana M et al., 2002, Cur It can be obtained by the method described in rBiol, vol. 12, pp. 735-739. In addition, "hsa-miR-30c-1-3p" has a hairpin-like structure as its precursor. "hsa-mir-30c-1" (miRBase Accession No. MI 0000736, SEQ ID NO: 421) is known.
[0282] As used herein, "hsa-miR-3621 gene" or "hsa-miR-3 The term "miR-3621" refers to the hsa-miR-3621 gene (miR-3621) set forth in SEQ ID NO: 204. RBase Accession No. MIMAT0018002) and other species The hsa-miR-3621 gene is a homologue or ortholog of the Wit By the method described in ten D et al., 2010, BMC Biol, Vol. 8, p. 58 Furthermore, "hsa-miR-3621" can be obtained by using a hairpin "hsa-mir-3621" (miRBase Accession No. o.MI0016012, sequence number 422) is known.
[0283] As used herein, "hsa-miR-6743-5p gene" or "hsa-mi The term "miR-6743-5p" refers to hsa-miR-6743 as set forth in SEQ ID NO: 205. -5p gene (miRBase Accession No. MIMAT0027387 ) and other species homologs or orthologs. The 3-5p genes are described in Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6743-5p has a hairpin-like structure as its precursor, hsa-mir -6743" (miRBase Accession No. MI0022588, sequence Number 423) is known.
[0284] As used herein, "hsa-miR-4298 gene" or "hsa-miR-4 The term "miR-4298" refers to the hsa-miR-4298 gene (mi RBase Accession No. MIMAT0016852) and other species The hsa-miR-4298 gene is a homologue or ortholog of Gof f By the method described in LA et al., 2009, PLoS One, Vol. 4, e7192 In addition, "hsa-miR-4298" can be obtained by using hairpin as its precursor. The miRBase Accession No. 10000126666444 has a phosphodiesterase-like structure, "hsa-mir-4298" (miRBase Accession No. 10000126666444). No. MI0015830, SEQ ID NO: 424) is known.
[0285] As used herein, "hsa-miR-4741 gene" or "hsa-miR-4 The term "miR-4741" refers to the hsa-miR-4741 gene (miR-4741) set forth in SEQ ID NO: 207. RBase Accession No. MIMAT0019871) and other species The hsa-miR-4741 gene is a homologue or ortholog. sson H et al., 2011, Cancer Res, Vol. 71, p78-86 Furthermore, "hsa-miR-4741" can be obtained by the method described above. The miRBase Accession No. 100012666644 (hsa-mir-4741) has a hairpin-like structure as a The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0017379, sequence number 425.
[0286] As used herein, "hsa-miR-3619-3p gene" or "hsa-mi The term "miR-3619-3p" refers to hsa-miR-3619 set forth in SEQ ID NO: 208. -3p gene (miRBase Accession No. MIMAT0019219 ) and other species homologs or orthologs. The 9-3p gene is described in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58 The miR-3619-3p gene can be obtained by the method described in " has a hairpin-like structure as its precursor "hsa-mir-3619" (miRB The enzyme (Accession No. MI0016009, SEQ ID NO: 426) is known There are.
[0287] As used herein, "hsa-miR-6824-5p gene" or "hsa-mi The term "miR-6824-5p" refers to hsa-miR-6824 set forth in SEQ ID NO: 209. -5p gene (miRBase Accession No. MIMAT0027548 ) and other species homologs or orthologs. The 4-5p genes are described in Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6824-5p has a hairpin-like structure as its precursor, hsa-mir -6824" (miRBase Accession No. MI0022669, sequence Number 427) is known.
[0288] As used herein, "hsa-miR-5698 gene" or "hsa-miR-5 The term "miR-5698" refers to the hsa-miR-5698 gene (miR-5698) set forth in SEQ ID NO: 210. RBase Accession No. MIMAT0022491) and other species The hsa-miR-5698 gene is a homologue or ortholog of the Wat Ahiki A et al., 2011, PLoS One, Vol. 6, e24950 hsa-miR-5698 can be obtained by the method described above. The miRBase Accession No. 100626666688 (hsa-mir-5698) forms a hairpin-like structure. ion No. MI0019305, SEQ ID NO: 428) is known.
[0289] As used herein, "hsa-miR-371a-5p gene" or "hsa-mi The term "miR-371a-5p" refers to hsa-miR-371a set forth in SEQ ID NO: 211. -5p gene (miRBase Accession No. MIMAT0004687 ) and other species homologs or orthologs. The a-5p gene is described in Suh MR et al., 2004, Dev Biol, vol. 270, p. 48 The miR-37 gene can be obtained by the method described in U.S. Pat. No. 6,849,868. 1a-5p" has a hairpin-like structure as its precursor, "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 429) is known.
[0290] As used herein, "hsa-miR-4488 gene" or "hsa-miR-4 The term "miR-4488" refers to the hsa-miR-4488 gene (miR-4488) set forth in SEQ ID NO: 212. RBase Accession No. MIMAT0019022) and other species The hsa-miR-4488 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4488" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4488" (miRBase Accession No. on No. MI0016849, SEQ ID NO: 430) is known.
[0291] As used herein, "hsa-miR-1233-5p gene" or "hsa-mi The term "miR-1233-5p" refers to hsa-miR-1233 as set forth in SEQ ID NO: 213. -5p gene (miRBase Accession No. MIMAT0022943 ) and other species homologs or orthologs. The 3-5p genes are described in Berezikov E et al., 2007, Mol Cell, vol. 28 It can be obtained by the method described in the "Hsa-mi R-1233-5p is a precursor of hsa-mir-1, which has a hairpin-like structure. 233-1”, “hsa-mir-1233-2” (miRBase Accessio n No. MI0006323, MI0015973, sequence numbers 431 and 432) are known It is being done.
[0292] As used herein, "hsa-miR-4723-5p gene" or "hsa-mi The term "miR-4723-5p" refers to hsa-miR-4723 set forth in SEQ ID NO: 214. -5p gene (miRBase Accession No. MIMAT0019838 ) and other species homologs or orthologs. The 3-5p gene is Persson H et al., 2011, Cancer Res, Vol. 71 The "hsa-miR- 4723-5p is a precursor of hsa-mir-472, which has a hairpin-like structure. 3" (miRBase Accession No. MI0017359, SEQ ID NO: 43 3) is known.
[0293] As used herein, "hsa-miR-24-3p gene" or "hsa-miR- The term "miR-24-3p" refers to the hsa-miR-24-3p gene set forth in SEQ ID NO: 215. (miRBase Accession No. MIMAT0000080) and other The hsa-miR-24-3p gene includes species homologs or orthologs. , Lagos-Quintana M et al., 2001, Science, Vol. 294, p. 8 53-858. 4-3p" has a hairpin-like structure as its precursor "hsa-mir-24-1", "hsa-mir-24-2" (miRBase Accession No. MI00 00080, MI0000081, SEQ ID NOs: 434, 435) are known.
[0294] As used herein, "hsa-miR-1238-5p gene" or "hsa-mi The term "miR-1238-5p" refers to hsa-miR-1238 as set forth in SEQ ID NO: 216. -5p gene (miRBase Accession No. MIMAT0022947 ) and other species homologs or orthologs. The 8-5p gene is described in Berezikov E et al., 2007, Mol Cell, vol. 28 It can be obtained by the method described in the "Hsa-mi R-1238-5p is a precursor of hsa-mir-1, which has a hairpin-like structure. 238" (miRBase Accession No. MI0006328, SEQ ID NO: 436) is known.
[0295] As used herein, "hsa-miR-4442 gene" or "hsa-miR-4 The term "miR-4442" refers to the hsa-miR-4442 gene (miR-4442) set forth in SEQ ID NO: 217. RBase Accession No. MIMAT0018960) and other species The hsa-miR-4442 gene is a homologue or ortholog of the Jim a Method described in DD et al., 2010, Blood, Vol. 116, p. e118-e127 Furthermore, "hsa-miR-4442" can be obtained as its precursor. The hairpin-like structure of "hsa-mir-4442" (miRBase Accession No. on No. MI0016785, SEQ ID NO: 437) is known.
[0296] As used herein, the term "hsa-miR-3928-3p gene" or "hsa-mi The term "miR-3928-3p" refers to hsa-miR-3928 as set forth in SEQ ID NO: 218. -3p gene (miRBase Accession No. MIMAT0018205 ) and other species homologs or orthologs. The 8-3p gene is Creighton CJ et al., 2010, PLoS One, Vol. 5 The "hsa-miR-3" can be obtained by the method described in e9637. 928-3p is a precursor of hsa-mir-3928, which has a hairpin-like structure. ” (miRBase Accession No. MI0016438, SEQ ID NO: 438 ) is known.
[0297] As used herein, "hsa-miR-6716-5p gene" or "hsa-mi The term "miR-6716-5p" refers to hsa-miR-6716 set forth in SEQ ID NO: 219. -5p gene (miRBase Accession No. MIMAT0025844 ) and other species homologs or orthologs. The 6-5p gene is described in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. It can be obtained by the method described in the specification. The precursor of miRBa is “hsa-mir-6716” (miRBa (Accession No. MI0022550, SEQ ID NO: 439) do.
[0298] As used herein, "hsa-miR-6089 gene" or "hsa-miR-6 The term "miR-6089" refers to the hsa-miR-6089 gene (miR-6089) set forth in SEQ ID NO: 220. RBase Accession No. MIMAT0023714) and other species The hsa-miR-6089 gene is a homologue or ortholog of the Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057 Furthermore, "hsa-miR-6089" can be obtained by the method described in Its precursors are "hsa-mir-6089-1" and "hsa- mir-6089-2” (miRBase Accession No. MI00203 66, MI0023563, SEQ ID NOs: 440, 441) are known.
[0299] As used herein, "hsa-miR-6124 gene" or "hsa-miR-6 The term "miR-6124" refers to the hsa-miR-6124 gene (miR-6124) set forth in SEQ ID NO: 221. RBase Accession No. MIMAT0024597) and other species The hsa-miR-6124 gene is a homologue or ortholog of the Smi th JL et al., 2012, J Virol, Vol. 86, p5278-5287 Furthermore, "hsa-miR-6124" can be obtained by the method described above. The miRBase Accession No. 10000124 (hsa-mir-6124) has a hairpin-like structure as a The sequence of the gene encoding the nucleotide sequence of the present invention is known to be nucleotide sequence no. MI0021258, sequence number 442.
[0300] As used herein, "hsa-miR-6778-5p gene" or "hsa-mi The term "miR-6778-5p" refers to hsa-miR-6778 as set forth in SEQ ID NO: 222. -5p gene (miRBase Accession No. MIMAT0027456 ) and other species homologs or orthologs. The 8-5p gene is Ladewig E et al., 2012, Genome Res, Vol. 22 It can be obtained by the method described in the above, pp. 1634-1645. miR-6778-5p has a hairpin-like structure as its precursor, hsa-mir -6778" (miRBase Accession No. MI0022623, sequence Number 443) is known.
[0301] As used herein, "hsa-miR-557 gene" or "hsa-miR-55 The term "miR-557" refers to the hsa-miR-557 gene (miRBa 7) set forth in SEQ ID NO: 223. se Accession No. MIMAT0003221) and other species homologs The hsa-miR-557 gene is a member of the Cummins JM et al., 2006, Proc Natl Acad Sci USA, vol. 103 It can be obtained by the method described in the "hsa- miR-557 has a hairpin-like structure as its precursor, hsa-mir-557 ” (miRBase Accession No. MI0003563, SEQ ID NO: 444 ) is known.
[0302] As used herein, "hsa-miR-6090 gene" or "hsa-miR-6 The term "miR-6090" refers to the hsa-miR-6090 gene (miR-6090) set forth in SEQ ID NO: 224. RBase Accession No. MIMAT0023715) and other species The hsa-miR-6090 gene is a homologue or ortholog of the Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057 Furthermore, "hsa-miR-6090" can be obtained by the method described in Its precursor, "hsa-mir-6090" (miRBase Accession No. MI0020367, SEQ ID NO: 445) is known.
[0303] As used herein, "hsa-miR-6757-5p gene" or "hsa-mi The term "miR-6757-5p" refers to hsa-miR-6757 as set forth in SEQ ID NO: 714. -5p gene (miRBase Accession No. MIMAT0027414 ) and other species homologs or orthologs. The 57-5p gene is described in Ladewig E et al., 2012, Genome Res., 2 It can be obtained by the method described in Vol. 2, pp. 1634-1645. a-miR-6757-5p has a hairpin-like structure as its precursor, hsa-m ir-6757” (miRBase Accession No. MI0022602, SEQ ID NO: 730) is known.
[0304] As used herein, "hsa-miR-4448 gene" or "hsa-miR-4 The term "miR-4448" refers to the hsa-miR-4448 gene (miR-4448) set forth in SEQ ID NO: 715. RBase Accession No. MIMAT0018967) and other species The hsa-miR-4448 gene is a homologue or ortholog of the Ji Ma DD et al., 2010, Blood, Vol. 116, e118-e127 hsa-miR-4448 can be obtained by the method described above. The miRBase Accession No. 1006266666 (hsa-mir-4448) forms a hairpin-like structure. ion No. MI0016791, SEQ ID NO: 731) is known.
[0305] As used herein, "hsa-miR-671-5p gene" or "hsa-miR The term "miR-671-5p" refers to hsa-miR-671-5p set forth in SEQ ID NO: 716. Gene (miRBase Accession No. MIMAT0003880) and This includes homologs or orthologs of hsa-miR-671-5 in other species. The p gene is described in Berezikov E et al., 2006, Genome Res, vol. 16, It can be obtained by the method described on pages 1289-1298. iR-671-5p is a precursor of hsa-mir-6, which has a hairpin-like structure. 71" (miRBase Accession No. MI0003760, SEQ ID NO: 7 32) is known.
[0306] As used herein, "hsa-miR-3178 gene" or "hsa-miR-3 The term "miR-3178" refers to the hsa-miR-3178 gene (miR-3178) set forth in SEQ ID NO: 717. RBase Accession No. MIMAT0015055) and other species The hsa-miR-3178 gene is a homologue or ortholog of the St The method described in ark MS et al., 2010, PLoS One, Vol. 5, e9685 hsa-miR-3178 can be obtained by The miRBase Accession No. hsa-mir-3178 (hsa-mir-3178) has an apin-like structure. n No. MI0014212, sequence number 733) is known.
[0307] As used herein, "hsa-miR-4725-3p gene" or "hsa-mi The term "miR-4725-3p" refers to hsa-miR-4725 set forth in SEQ ID NO: 718. -3p gene (miRBase Accession No. MIMAT0019844 ) and other species homologs or orthologs. The 25-3p gene is Persson H et al., 2011, Cancer Res, 71 The hsa-miR can be obtained by the method described in Vol. -4725-3p is a precursor of hsa-mir-47, which has a hairpin-like structure. 25" (miRBase Accession No. MI0017362, SEQ ID NO: 7 34) is known.
[0308] As used herein, "hsa-miR-940 gene" or "hsa-miR-94 The term "miR-940" refers to the hsa-miR-940 gene (miRBa se Accession No. MIMAT0004983) and other species homologs The hsa-miR-940 gene is a gene encoding miR-940. et al., 2007, A Cancer Res., Vol. 67, p. 6031-6043 hsa-miR-940 can be obtained by the method described above. The miRBase Accession No. 100001266664 ... sion No. MI0005762, SEQ ID NO: 735) is known.
[0309] As used herein, "hsa-miR-6789-5p gene" or "hsa-mi The term "miR-6789-5p" refers to hsa-miR-6789 set forth in SEQ ID NO: 720. -5p gene (miRBase Accession No. MIMAT0027478 ) and other species homologs or orthologs. The 89-5p gene is described in Ladewig E et al., 2012, Genome Res., 2 2, pp. 1634-1645. a-miR-6789-5p has a hairpin-like structure as its precursor, hsa-m ir-6789” (miRBase Accession No. MI0022634, SEQ ID NO: 736) is known.
[0310] As used herein, "hsa-miR-4484 gene" or "hsa-miR-4 The term "miR-4484" refers to the hsa-miR-4484 gene (miR-4484) set forth in SEQ ID NO: 721. RBase Accession No. MIMAT0019018) and other species The hsa-miR-4484 gene is a homologue or ortholog. Ma DD et al., 2010, Blood., Vol. 116, e118-e127 hsa-miR-4484 can be obtained by the method described above. The miRBase Accession No. 1000012666666, which forms a hairpin-like structure, is sion No. MI0016845, SEQ ID NO: 737) is known.
[0311] As used herein, "hsa-miR-4634 gene" or "hsa-miR-4 The term "miR-4634" refers to the hsa-miR-4634 gene (miR-4634) set forth in SEQ ID NO: 722. RBase Accession No. MIMAT0019691) and other species The hsa-miR-4634 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res., Vol. 71, p. 78-86 hsa-miR-4634 can be obtained by the method described above. The miRBase Ac receptor has a hairpin-like structure as a precursor protein, hsa-mir-4634 (miRBase Ac Accession No. MI0017261, SEQ ID NO: 738) is known.
[0312] As used herein, "hsa-miR-4745-5p gene" or "hsa-mi The term "miR-4745-5p" refers to hsa-miR-4745 as set forth in SEQ ID NO: 723. -5p gene (miRBase Accession No. MIMAT0019878 ) and other species homologs or orthologs. The 45-5p gene is described in Persson H et al., 2011, Cancer Res, 71 The hsa-miR can be obtained by the method described in Vol. -4745-5p is a precursor of hsa-mir-47, which has a hairpin-like structure. 45" (miRBase Accession No. MI0017384, SEQ ID NO: 7 39) is known.
[0313] As used herein, "hsa-miR-4730 gene" or "hsa-miR-4 The term "miR-4730" refers to the hsa-miR-4730 gene (miR-4730) set forth in SEQ ID NO: 724. RBase Accession No. MIMAT0019852) and other species The hsa-miR-4730 gene is a homologue or ortholog of the rsson H et al., 2011, Cancer Res, Vol. 71, p78-86 hsa-miR-4730 can be obtained by the method described above. The miRBase Accelerator has a hairpin-like structure called "hsa-mir-4730" ( Session No. MI0017367, SEQ ID NO: 740) is known.
[0314] As used herein, "hsa-miR-6803-5p gene" or "hsa-mi The term "miR-6803-5p" refers to hsa-miR-6803 set forth in SEQ ID NO: 725. -5p gene (miRBase Accession No. MIMAT0027506 ) and other species homologs or orthologs. The 03-5p gene is described in Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6803-5p has a hairpin-like structure as its precursor, "hsa-mi r-6803” (miRBase Accession No. MI0022648, Column number 741) is known.
[0315] As used herein, "hsa-miR-6798-5p gene" or "hsa-mi The term "miR-6798-5p" refers to hsa-miR-6798 as set forth in SEQ ID NO: 726. -5p gene (miRBase Accession No. MIMAT0027496 ) and other species homologs or orthologs. The 98-5p gene is Ladewig E et al., 2012, Genome Res, 22 It can be obtained by the method described in Vol. 1, pp. 1634-1645. -miR-6798-5p has a hairpin-like structure as its precursor, "hsa-mi r-6798” (miRBase Accession No. MI0022643, Column number 742) is known.
[0316] As used herein, "hsa-miR-3648 gene" or "hsa-miR-3 The term "miR-3648" refers to the hsa-miR-3648 gene (miR-3648) set forth in SEQ ID NO: 727. RBase Accession No. MIMAT0018068) and other species The hsa-miR-3648 gene is a homologue or ortholog of the Me Iri E et al., 2010, Nucleic Acids Res, Vol. 38, p. 6234 The miR-36 can be obtained by the method described in US Pat. No. 6,246,624. 48" has a hairpin-like structure as its precursor, "hsa-mir-3648" (mi RBase Accession No. MI0016048, sequence number 743) It is being done.
[0317] As used herein, "hsa-miR-4783-3p gene" or "hsa-mi The term "miR-4783-3p" refers to hsa-miR-4783 set forth in SEQ ID NO: 728. -3p gene (miRBase Accession No. MIMAT0019947 ) and other species homologs or orthologs. The 83-3p gene is described in Persson H et al., 2011, Cancer Res, 71 The hsa-miR can be obtained by the method described in Vol. -4783-3p is a precursor of hsa-mir-47, which has a hairpin-like structure. 83" (miRBase Accession No. MI0017428, SEQ ID NO: 7 44) is known.
[0318] As used herein, the term "hsa-miR-6836-3p gene" or "hsa-mi The term "miR-6836-3p" refers to hsa-miR-6836 set forth in SEQ ID NO: 729. -3p gene (miRBase Accession No. MIMAT0027575 ) and other species homologs or orthologs. The 36-3p gene is described in Ladewig E et al., 2012, Genome Res., 2 2, pp. 1634-1645. a-miR-6836-3p has a hairpin-like structure as its precursor, hsa-m ir-6836” (miRBase Accession No. MI0022682, SEQ ID NO: 745) is known.
[0319] In addition, mature miRNAs are formed from RNA precursors with hairpin-like structures. When excised as A, one to several bases before and after the sequence may be excised shorter or longer, Base substitutions can occur, resulting in mutants, called isomiRs (Morin R D. et al., 2008, Genome Res., Vol. 18, pp. 610-621). In RBase Release 20, any of SEQ ID NOs: 1 to 224 and 714 to 729 In addition to the base sequences shown above, there are numerous isomiRs, such as those shown in SEQ ID NOs: 446 to 713. Variants and fragments of the nucleotide sequences represented by any of nucleotides 746 to 765 are also shown. These mutants also contain a base represented by any one of SEQ ID NOs: 1 to 224 and 714 to 729. It can be obtained as miRNA having the sequence.
[0320] That is, SEQ ID NOs: 1, 3, 4, 6, 7, 10, 11, 13, 14, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37 7, 20, 22, 26, 29, 36, 38, 39, 40, 42, 43, 44, 46, 49 , 52, 59, 60, 62, 63, 65, 66, 67, 72, 76, 77, 78, 81, 83, 84, 85, 86, 87, 88, 89, 90, 92, 93, 94, 96, 100, 103, 105, 106, 107, 113, 114, 115, 116, 117, 118, 119, 120, 121, 123, 124, 125, 126, 130, 132, 134, 136, 139, 140, 141, 142, 143, 144, 145, 147, 148, 150, 151, 152, 155, 157, 158, 159, 163, 164, 165, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 187, 189, 191, 192, 193, 195, 196, 198, 200, 201, 202, 203, 206, 207, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 221, 715, 716, 717, 718, 719, 721, 723, 724, 727 and 728 or the base sequence in which u is t, a variant of a polynucleotide consisting of a base sequence, for example, miRBase The longest variants registered in Release 20 are SEQ ID NO: 446 , 448, 450, 452, 454, 456, 458, 460, 462, 464, 466 , 468, 470, 472, 474, 476, 478, 480, 482, 484, 486 , 488, 490, 492, 494, 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, 558, 560, 562, 564, 566 , 568, 570, 572, 574, 576, 578, 580, 582, 584, 586 , 588, 590, 592, 594, 596, 598, 600, 602, 604, 606 , 608, 610, 612, 614, 616, 618, 620, 622, 624, 626 , 628, 630, 632, 634, 636, 638, 640, 642, 644, 646 , 648, 650, 652, 654, 656, 658, 660, 662, 664, 666 , 668, 670, 672, 674, 676, 678, 680, 682, 684, 686 , 688, 690, 692, 694, 696, 698, 700, 702, 704, 706 , 708, 710, 712, 746, 748, 750, 752, 754, 756, 758 , 760, 762 and 764.
[0321] In addition, the sequences of SEQ ID NOs: 1, 3, 4, 6, 7, 10, 11, 13, 14, 16, 17, 20, 22, 26, 29, 36, 38, 39, 40, 42, 43, 44, 46, 49, 5 2, 59, 60, 62, 63, 65, 66, 67, 72, 76, 77, 78, 81, 83 , 84, 85, 86, 87, 88, 89, 90, 92, 93, 94, 96, 100, 10 3, 105, 106, 107, 113, 114, 115, 116, 117, 118, 11 9, 120, 121, 123, 124, 125, 126, 130, 132, 134, 13 6, 139, 140, 141, 142, 143, 144, 145, 147, 148, 15 0, 151, 152, 155, 157, 158, 159, 163, 164, 165, 16 7, 168, 169, 170, 171, 172, 173, 174, 175, 176, 17 7, 178, 179, 180, 181, 182, 183, 184, 185, 187, 18 9, 191, 192, 193, 195, 196, 198, 200, 201, 202, 20 3, 206, 207, 210, 211, 212, 213, 214, 215, 217, 21 8, 219, 220, 221, 715, 716, 717, 718, 719, 721, 72 3, 724, 727 and 728, or the base sequences in which u is t Among the variants of polynucleotides consisting of a certain base sequence, for example, miRBase Re The shortest variants registered in the nucleotide sequence 20 are SEQ ID NOs: 447 and 4 49, 451, 453, 455, 457, 459, 461, 463, 465, 467, 4 69, 471, 473, 475, 477, 479, 481, 483, 485, 487, 4 89, 491, 493, 495, 497, 499, 501, 503, 505, 507, 5 09, 511, 513, 515, 517, 519, 521, 523, 525, 527, 5 29, 531, 533, 535, 537, 539, 541, 543, 545, 547, 5 49, 551, 553, 555, 557, 559, 561, 563, 565, 567, 5 69, 571, 573, 575, 577, 579, 581, 583, 585, 587, 5 89, 591, 593, 595, 597, 599, 601, 603, 605, 607, 6 09, 611, 613, 615, 617, 619, 621, 623, 625, 627, 6 29, 631, 633, 635, 637, 639, 641, 643, 645, 647, 6 49, 651, 653, 655, 657, 659, 661, 663, 665, 667, 6 69, 671, 673, 675, 677, 679, 681, 683, 685, 687, 6 89, 691, 693, 695, 697, 699, 701, 703, 705, 707, 7 09, 711, 713, 747, 749, 751, 753, 755, 757, 759, 7 Examples of the polynucleotides include those having the sequences represented by nucleotides 61, 763 and 765.
[0322] In addition to these variants and fragments, the sequences of SEQ ID NOs: 1 to 5 registered in miRBase are also included. Examples of polynucleotides that are isomiRs include 224 and 714-729. Furthermore, a polypeptide containing a base sequence represented by any one of SEQ ID NOs: 1 to 224 and 714 to 729 Examples of oligonucleotides include the precursors SEQ ID NOs: 225-445 and 730, respectively. Examples of the polynucleotide include those represented by any one of the following:
[0323] Names of genes represented by SEQ ID NOs: 1 to 765 and miRBase Accession Numbers The registration numbers are listed in Table 1.
[0324] As used herein, the term "capable of specifically binding" refers to the nucleic acid probe or probe used in the present invention. This means that the primer binds to a specific target nucleic acid and is substantially incapable of binding to other nucleic acids. .
[0325] [Table 1] TIFF0007810373000002.tif248108TIFF0007810373000003.tif248107TIFF0007810373000004.tif 247106TIFF0007810373000005.tif248107TIFF0007810373000006.tif247106TIFF00078103730000 07.tif247107TIFF0007810373000008.tif247107TIFF0007810373000009.tif247108TIFF00078103 73000010.tif247108TIFF0007810373000011.tif247109TIFF0007810373000012.tif246107TIFF00 07810373000013.tif246107TIFF0007810373000014.tif246108TIFF0007810373000015.tif247107 TIFF0007810373000016.tif246107TIFF0007810373000017.tif247107TIFF0007810373000018.tif 246109TIFF0007810373000019.tif246107TIFF0007810373000020.tif246108TIFF0007810373000021.tif247108TIFF0007810373000022.tif23107This specification is based on the specification and The contents shown in the drawings are included. [Effects of the Invention]
[0326] The present invention makes it possible to detect liver cancer easily and with high accuracy. refers to measurements of several miRNAs in patients' blood, serum, and / or plasma that can be collected minimally invasively. This can be used as a target to easily detect whether a patient has liver cancer. [Brief explanation of the drawings]
[0327] [Figure 1] This figure shows the relationship between the base sequences of hsa-miR-1343-5p, represented by sequence number 131, which is generated from its precursor hsa-mir-1343, represented by sequence number 225, and hsa-miR-1343-3p, represented by sequence number 1. [Figure 2] Left: The vertical axis shows the measured values of hsa-miR-1343-3p (SEQ ID NO: 1) for healthy subjects (100 individuals) and liver cancer patients (34 individuals) selected as the training sample group. The horizontal line in the figure indicates the threshold (7.09) for discriminating between the two groups, optimized by Fisher's discriminant analysis. Right: The vertical axis shows the measured values of hsa-miR-1343-3p (SEQ ID NO: 1) for healthy subjects (50 individuals) and liver cancer patients (16 individuals) selected as the test sample group. The horizontal line in the figure indicates the threshold (7.09) for discriminating between the two groups, set in the training sample group. [Figure 3] Left: The horizontal axis shows the measured values of hsa-miR-1343-3p (SEQ ID NO: 1) and the vertical axis shows the measured values of hsa-miR-6726-5p (SEQ ID NO: 2) for healthy individuals (100 individuals, circles) and liver cancer patients (34 individuals, triangles) selected as the training sample group. The line in the figure represents the discriminant function (0 = 0.77x + y - 15.07) optimized by Fisher's discriminant analysis to discriminate between the two groups. Right: The horizontal axis shows the measured values of hsa-miR-1343-3p (SEQ ID NO: 1) and the vertical axis shows the measured values of hsa-miR-6726-5p (SEQ ID NO: 2) for healthy individuals (50 individuals, circles) and liver cancer patients (16 individuals, triangles) selected as the test sample group. The line in the figure represents the threshold (0 = 0.77x + y - 15.07) for discriminating between the two groups, set in the training sample group. [Figure 4] Upper figure: hsa-miR-6131 (SEQ ID NO: 7), hsa-miR-642a-3p (SEQ ID NO: 148), hsa-miR-7641 (SEQ ID NO: 9), and hsa-miR-7641 (SEQ ID NO: 9) were selected as the training sample group. These included 35 liver cancer patients, 99 healthy individuals, 72 pancreatic cancer patients, 61 biliary tract cancer patients, 35 colorectal cancer patients, 38 gastric cancer patients, 25 esophageal cancer patients, and 16 patients with benign pancreatic and biliary diseases. A discriminant equation was created using Fisher's discriminant analysis from the measured values of miR-6729-5p (SEQ ID NO: 27) (0.88xhsa-miR-6131-1.58xhsa-miR-642a-3p+0.39xhsa-miR-7641-0.33xhsa-miR-6729-5p+5.19), and the discriminant score obtained from the discriminant equation is plotted on the vertical axis and the sample group on the horizontal axis. The dotted line in the figure indicates the discriminant boundary for discriminating between the two groups where the discriminant score is 0. The figure below shows the measured values of hsa-miR-6131 (SEQ ID NO: 7), hsa-miR-642a-3p (SEQ ID NO: 148), hsa-miR-7641 (SEQ ID NO: 9), and hsa-miR-6729-5p (SEQ ID NO: 27) for the test sample group: 17 liver cancer patients, 51 healthy subjects, 28 pancreatic cancer patients, 37 biliary tract cancer patients, 15 colorectal cancer patients, 12 gastric cancer patients, 25 esophageal cancer patients, and 5 patients with benign pancreatic and biliary diseases. The discriminant scores obtained from the discriminant equation for the training sample group are plotted on the vertical axis, and the sample group is plotted on the horizontal axis. The dotted line in the figure indicates the discriminant boundary for distinguishing between the two groups, where the discriminant score is 0. DETAILED DESCRIPTION OF THE INVENTION
[0328] The present invention will be described in more detail below.
[0329] 1. Target nucleic acids for liver cancer Using the nucleic acid probe or primer for detecting liver cancer defined above of the present invention, as a liver cancer marker for detecting the presence and / or absence of liver cancer or liver cancer cells; The main target nucleic acids of miR-1343-3p, miR-6726- 5p、hsa-miR-6515-3p、hsa-miR-4651、hsa-miR- 4257、hsa-miR-3188、hsa-miR-6131、hsa-miR-6 766-3p、hsa-miR-7641、hsa-miR-1249、hsa-miR -3679-3p、hsa-miR-6787-5p、hsa-miR-4454、hs a-miR-3135b, hsa-miR-6765-3p, hsa-miR-7975 hsa-miR-204-3p hsa-miR-7977 hsa-miR-711 0-5p、hsa-miR-6717-5p、hsa-miR-6870-5p、hsa -miR-663b、hsa-miR-6875-5p、hsa-miR-8072、h sa-miR-6816-5p, hsa-miR-4281, hsa-miR-6729 -5p, hsa-miR-8069, hsa-miR-4706, hsa-miR-71 08-5p、hsa-miR-4433b-3p、hsa-miR-6893-5p、h sa-miR-6857-5p, hsa-miR-1227-5p, hsa-miR-6 741-5p, hsa-miR-451a, hsa-miR-8063, hsa-miR -3622a-5p、hsa-miR-615-5p、hsa-miR-128-1-5 p、hsa-miR-6825-5p、hsa-miR-1260b、hsa-miR- 4433-3p、hsa-miR-4665-5p、hsa-miR-7845-5p、 hsa-miR-1908-5p, hsa-miR-6840-3p, hsa-miR- 6765-5p、hsa-miR-296-5p、hsa-miR-3675-3p、h sa-miR-6781-5p, hsa-miR-423-5p, hsa-miR-36 63-3p、hsa-miR-6784-5p、hsa-miR-6749-5p、hs a-miR-1231、hsa-miR-4746-3p、hsa-miR-6780b -5p、hsa-miR-4758-5p、hsa-miR-3679-5p、hsa- miR-3184-5p, hsa-miR-6125, hsa-miR-6721-5p hsa-miR-6791-5p hsa-miR-3185 hsa-miR-12 60a, hsa-miR-3197, hsa-miR-6845-5p, hsa-miR -6887-5p、hsa-miR-6738-5p、hsa-miR-6872-3p hsa-miR-4497 hsa-miR-1229-5p hsa-miR-68 20-5p、hsa-miR-6777-5p、hsa-miR-3917、hsa-m iR-5787, hsa-miR-4286, hsa-miR-6877-5p, hsa -miR-1225-3p、hsa-miR-6088、hsa-miR-6800-5 p、hsa-miR-1246、hsa-miR-4467、hsa-miR-4419 b、hsa-miR-1914-3p、hsa-miR-4632-5p、hsa-mi R-1915-5p、hsa-miR-3940-5p、hsa-miR-1185-2 -3p、hsa-miR-6746-5p、hsa-miR-5001-5p、hsa- miR-1228-5p, hsa-miR-5572, hsa-miR-4327, hs a-miR-4638-5p, hsa-miR-6799-5p, hsa-miR-68 61-5p、hsa-miR-6727-5p、hsa-miR-4513、hsa-m iR-6805-3p, hsa-miR-6808-5p, hsa-miR-4449 hsa-miR-1199-5p, hsa-miR-1275, hsa-miR-479 2、hsa-miR-4443、hsa-miR-6891-5p、hsa-miR-6 826-5p、hsa-miR-6807-5p、hsa-miR-7150、hsa- miR-4534, hsa-miR-4476, hsa-miR-4649-5p, hs a-miR-4525、hsa-miR-1915-3p、hsa-miR-4516、 hsa-miR-4417, hsa-miR-642b-3p, hsa-miR-314 1、hsa-miR-5100、hsa-miR-6848-5p、hsa-miR-4 739、hsa-miR-4459、hsa-miR-1237-5p、hsa-miR -296-3p、hsa-miR-4665-3p、hsa-miR-6786-5p、 hsa-miR-4258, hsa-miR-6510-5p, hsa-miR-134 3-5p、hsa-miR-1247-3p、hsa-miR-6805-5p、hsa -miR-4492、hsa-miR-1469、hsa-miR-1268b、hsa -miR-6858-5p、hsa-miR-3937、hsa-miR-939-5p hsa-miR-3656 hsa-miR-744-5p hsa-miR-468 7-3p、hsa-miR-4763-3p、hsa-miR-3620-5p、hsa -miR-3195、hsa-miR-6842-5p、hsa-miR-4707-5 p, hsa-miR-642a-3p, hsa-miR-7113-3p, hsa-mi R-4728-5p, hsa-miR-5195-3p, hsa-miR-1185-1 -3p, hsa-miR-6774-5p, hsa-miR-8059, hsa-miR -3131, hsa-miR-7847-3p, hsa-miR-4463, hsa-m iR-128-2-5p, hsa-miR-4508, hsa-miR-6806-5p , hsa-miR-7111-5p, hsa-miR-6782-5p, hsa-miR -4734, hsa-miR-3162-5p, hsa-miR-887-3p, hsa -miR-6752-5p, hsa-miR-6724-5p, hsa-miR-675 7-5p, hsa-miR-4448, hsa-miR-671-5p, hsa-miR -3178, hsa-miR-4725-3p, hsa-miR-940, hsa-mi R-6789-5p, hsa-miR-4484, hsa-miR-4634, hsa- miR-4745-5p, hsa-miR-4730, hsa-miR-6803-5p , hsa-miR-6798-5p, hsa-miR-3648, hsa-miR-47 at least one selected from the group consisting of miR-6836-3p and hsa-miR-6836-3p More than one miRNA can be used. Other liver cancer markers that can be used include hsa-miR-23b-3p, hsa- miR-23a-3p, hsa-miR-625-3p, hsa-miR-1228-3 p, hsa-miR-614, hsa-miR-1913, hsa-miR-92a-2 -5p, hsa-miR-187-5p, hsa-miR-16-5p, hsa-miR -92b-3p, hsa-miR-150-3p, hsa-miR-564, hsa-m iR-125a-3p, hsa-miR-92b-5p, hsa-miR-92a-3p and at least one miRN selected from the group consisting of hsa-miR-663a A can also be preferably used as a target nucleic acid. Other liver cancer markers that can be used include hsa-miR-4688, hsa -miR-4648, hsa-miR-6085, hsa-miR-6126, hsa- miR-6880-5p, hsa-miR-328-5p, hsa-miR-6768- 5p, hsa-miR-3180, hsa-miR-6087, hsa-miR-127 3g-3p, hsa-miR-1225-5p, hsa-miR-3196, hsa-m iR-4695-5p, hsa-miR-6732-5p, hsa-miR-638, h sa-miR-6813-5p, hsa-miR-665, hsa-miR-486-3 p, hsa-miR-4466, hsa-miR-30c-1-3p, hsa-miR- 3621, hsa-miR-6743-5p, hsa-miR-4298, hsa-mi R-4741, hsa-miR-3619-3p, hsa-miR-6824-5p, h sa-miR-5698, hsa-miR-371a-5p, hsa-miR-4488 , hsa-miR-1233-5p, hsa-miR-4723-5p, hsa-miR -24-3p, hsa-miR-1238-5p, hsa-miR-4442, hsa- miR-3928-3p, hsa-miR-6716-5p, hsa-miR-6089 , hsa-miR-6124, hsa-miR-6778-5p, hsa-miR-55 At least one or more miRs selected from the group consisting of miR-7 and hsa-miR-6090 NA can also be preferably used as the target nucleic acid.
[0330] The above miRNAs include, for example, any of SEQ ID NOs: 1 to 224 and 714 to 729. Human genes containing the base sequences represented by the miR-1343- 3p, hsa-miR-6726-5p, hsa-miR-6515-3p, hsa-m iR-4651, hsa-miR-4257, hsa-miR-3188, hsa-mi R-6131, hsa-miR-6766-3p, hsa-miR-7641, hsa- miR-1249, hsa-miR-3679-3p, hsa-miR-6787-5p , hsa-miR-4454, hsa-miR-3135b, hsa-miR-6765 -3p, hsa-miR-7975, hsa-miR-204-3p, hsa-miR- 7977, hsa-miR-7110-5p, hsa-miR-6717-5p, hsa -miR-6870-5p, hsa-miR-663b, hsa-miR-6875-5 p, hsa-miR-8072, hsa-miR-6816-5p, hsa-miR-4 281, hsa-miR-6729-5p, hsa-miR-8069, hsa-miR -4706, hsa-miR-7108-5p, hsa-miR-4433b-3p, h sa-miR-6893-5p, hsa-miR-6857-5p, hsa-miR-1 227-5p, hsa-miR-6741-5p, hsa-miR-451a, hsa- miR-8063, hsa-miR-3622a-5p, hsa-miR-615-5p , hsa-miR-128-1-5p, hsa-miR-6825-5p, hsa-mi R-1260b、hsa-miR-4433-3p、hsa-miR-4665-5p、 hsa-miR-7845-5p、hsa-miR-1908-5p、hsa-miR- 6840-3p、hsa-miR-6765-5p、hsa-miR-296-5p、h sa-miR-3675-3p, hsa-miR-6781-5p, hsa-miR-4 23-5p、hsa-miR-3663-3p、hsa-miR-6784-5p、hs a-miR-6749-5p、hsa-miR-1231、hsa-miR-4746- 3p、hsa-miR-6780b-5p、hsa-miR-4758-5p、hsa- miR-3679-5p, hsa-miR-3184-5p, hsa-miR-6125 hsa-miR-6721-5p hsa-miR-6791-5p hsa-miR -3185, hsa-miR-1260a, hsa-miR-3197, hsa-miR -6845-5p、hsa-miR-6887-5p、hsa-miR-6738-5p hsa-miR-6872-3p hsa-miR-4497 hsa-miR-12 29-5p、hsa-miR-6820-5p、hsa-miR-6777-5p、hs a-miR-3917、hsa-miR-5787、hsa-miR-4286、hsa -miR-6877-5p、hsa-miR-1225-3p、hsa-miR-608 8、hsa-miR-6800-5p、hsa-miR-1246、hsa-miR-4 467、hsa-miR-4419b、hsa-miR-1914-3p、hsa-mi R-4632-5p、hsa-miR-1915-5p、hsa-miR-3940-5 p、hsa-miR-1185-2-3p、hsa-miR-6746-5p、hsa- miR-5001-5p, hsa-miR-1228-5p, hsa-miR-5572 hsa-miR-4327 hsa-miR-4638-5p hsa-miR-67 99-5p、hsa-miR-6861-5p、hsa-miR-6727-5p、hs a-miR-4513、hsa-miR-6805-3p、hsa-miR-6808- 5p、hsa-miR-4449、hsa-miR-1199-5p、hsa-miR- 1275、hsa-miR-4792、hsa-miR-4443、hsa-miR-6 891-5p、hsa-miR-6826-5p、hsa-miR-6807-5p、h sa-miR-7150, hsa-miR-4534, hsa-miR-4476, hs a-miR-4649-5p, hsa-miR-4525, hsa-miR-1915- 3p、hsa-miR-4516、hsa-miR-4417、hsa-miR-642 b-3p, hsa-miR-3141, hsa-miR-5100, hsa-miR-6 848-5p, hsa-miR-4739, hsa-miR-4459, hsa-miR -1237-5p、hsa-miR-296-3p、hsa-miR-4665-3p、 hsa-miR-6786-5p, hsa-miR-4258, hsa-miR-651 0-5p、hsa-miR-1343-5p、hsa-miR-1247-3p、hsa -miR-6805-5p、hsa-miR-4492、hsa-miR-1469、h sa-miR-1268b, hsa-miR-6858-5p, hsa-miR-393 7、hsa-miR-939-5p、hsa-miR-3656、hsa-miR-74 4-5p、hsa-miR-4687-3p、hsa-miR-4763-3p、hsa -miR-3620-5p、hsa-miR-3195、hsa-miR-6842-5 p、hsa-miR-4707-5p、hsa-miR-642a-3p、hsa-mi R-7113-3p, hsa-miR-4728-5p, hsa-miR-5195-3 p、hsa-miR-1185-1-3p、hsa-miR-6774-5p、hsa- miR-8059, hsa-miR-3131, hsa-miR-7847-3p, hs a-miR-4463, hsa-miR-128-2-5p, hsa-miR-4508 hsa-miR-6806-5p hsa-miR-7111-5p hsa-miR -6782-5p、hsa-miR-4734、hsa-miR-3162-5p、hs a-miR-887-3p, hsa-miR-6752-5p, hsa-miR-672 4-5p、hsa-miR-6757-5p、hsa-miR-4448、hsa-mi R-671-5p、hsa-miR-3178、hsa-miR-4725-3p、hs a-miR-940, hsa-miR-6789-5p, hsa-miR-4484, h sa-miR-4634, hsa-miR-4745-5p, hsa-miR-4730 hsa-miR-6803-5p hsa-miR-6798-5p hsa-miR -3648、hsa-miR-4783-3p、hsa-miR-6836-3p、hs a-miR-23b-3p、hsa-miR-23a-3p、hsa-miR-625- 3p、hsa-miR-1228-3p、hsa-miR-614、hsa-miR-1 913、hsa-miR-92a-2-5p、hsa-miR-187-5p、hsa- miR-16-5p, hsa-miR-92b-3p, hsa-miR-150-3p, hsa-miR-564, hsa-miR-125a-3p, hsa-miR-92b- 5p, hsa-miR-92a-3p, hsa-miR-663a, hsa-miR-4 688, hsa-miR-4648, hsa-miR-6085, hsa-miR-61 26, hsa-miR-6880-5p, hsa-miR-328-5p, hsa-mi R-6768-5p, hsa-miR-3180, hsa-miR-6087, hsa- miR-1273g-3p, hsa-miR-1225-5p, hsa-miR-319 6, hsa-miR-4695-5p, hsa-miR-6732-5p, hsa-mi R-638, hsa-miR-6813-5p, hsa-miR-665, hsa-mi R-486-3p, hsa-miR-4466, hsa-miR-30c-1-3p, h sa-miR-3621, hsa-miR-6743-5p, hsa-miR-4298 、hsa-miR-4741, hsa-miR-3619-3p, hsa-miR-68 24-5p, hsa-miR-5698, hsa-miR-371a-5p, hsa-m iR-4488, hsa-miR-1233-5p, hsa-miR-4723-5p, hsa-miR-24-3p, hsa-miR-1238-5p, hsa-miR-44 42, hsa-miR-3928-3p, hsa-miR-6716-5p, hsa-m iR-6089, hsa-miR-6124, hsa-miR-6778-5p, hsa -miR-557 and hsa-miR-6090), its homologs, its transcriptional products, and those Here, genes, homologs, transcripts, variants and derivatives are included. is as defined above.
[0331] A preferred target nucleic acid is a human gene comprising a base sequence represented by any one of SEQ ID NOs: 1 to 765. A gene or its transcription product, more preferably, the transcription product, i.e., miRNA, The miRNA is a precursor RNA of the miRNA, pri-miRNA or pre-miRNA.
[0332] The first target gene is the hsa-miR-1343-3p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0333] The second target gene is the hsa-miR-6726-5p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0334] The third target gene is the hsa-miR-6515-3p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0335] The fourth target gene is the hsa-miR-4651 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof, has not been There are no known reports that altered expression of these substances can be markers for liver cancer.
[0336] The fifth target gene is the hsa-miR-4257 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof, has not been There are no known reports that altered expression of these substances can be markers for liver cancer.
[0337] The sixth target gene is the hsa-miR-3188 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof, has not been There are no known reports that altered expression of these substances can be markers for liver cancer.
[0338] The seventh target gene is the hsa-miR-6131 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof, has not been There are no known reports that altered expression of these substances can be markers for liver cancer.
[0339] The eighth target gene is the hsa-miR-6766-3p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0340] The ninth target gene is the hsa-miR-7641 gene, its homologs, and their transcription factors. The gene or its transcript, or a variant or derivative thereof, has not been There are no known reports that altered expression of these substances can be markers for liver cancer.
[0341] The tenth target gene is the hsa-miR-1249 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0342] The eleventh target gene is the hsa-miR-3679-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0343] The 12th target gene is the hsa-miR-6787-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0344] The 13th target gene is the hsa-miR-4454 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0345] The 14th target gene is the hsa-miR-3135b gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0346] The 15th target gene is the hsa-miR-6765-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0347] The 16th target gene is the hsa-miR-7975 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0348] The 17th target gene is the hsa-miR-204-3p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0349] The 18th target gene is the hsa-miR-7977 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0350] The 19th target gene is the hsa-miR-7110-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0351] The 20th target gene is the hsa-miR-6717-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0352] The 21st target gene is the hsa-miR-6870-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0353] The 22nd target gene is the hsa-miR-663b gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0354] The 23rd target gene is the hsa-miR-6875-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0355] The 24th target gene is the hsa-miR-8072 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0356] The 25th target gene is the hsa-miR-6816-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0357] The 26th target gene is the hsa-miR-4281 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0358] The 27th target gene is the hsa-miR-6729-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0359] The 28th target gene is the hsa-miR-8069 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0360] The 29th target gene is the hsa-miR-4706 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0361] The 30th target gene is the hsa-miR-7108-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0362] The 31st target gene is the hsa-miR-4433b-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0363] The 32nd target gene is the hsa-miR-6893-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0364] The 33rd target gene is the hsa-miR-6857-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0365] The 34th target gene is the hsa-miR-1227-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0366] The 35th target gene is the hsa-miR-6741-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0367] The 36th target gene is the hsa-miR-451a gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0368] The 37th target gene is the hsa-miR-8063 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0369] The 38th target gene is the hsa-miR-3622a-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0370] The 39th target gene is the hsa-miR-615-5p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0371] The 40th target gene is the hsa-miR-128-1-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0372] The 41st target gene is the hsa-miR-6825-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0373] The 42nd target gene is the hsa-miR-1260b gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0374] The 43rd target gene is the hsa-miR-4433-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0375] The 44th target gene is the hsa-miR-4665-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0376] The 45th target gene is the hsa-miR-7845-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0377] The 46th target gene is the hsa-miR-1908-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0378] The 47th target gene is the hsa-miR-6840-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0379] The 48th target gene is the hsa-miR-6765-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0380] The 49th target gene is the hsa-miR-296-5p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0381] The 50th target gene is the hsa-miR-3675-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0382] The 51st target gene is the hsa-miR-6781-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0383] The 52nd target gene is the hsa-miR-423-5p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0384] The 53rd target gene is the hsa-miR-3663-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0385] The 54th target gene is the hsa-miR-6784-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0386] The 55th target gene is the hsa-miR-6749-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0387] The 56th target gene is the hsa-miR-1231 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0388] The 57th target gene is the hsa-miR-4746-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0389] The 58th target gene is the hsa-miR-6780b-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0390] The 59th target gene is the hsa-miR-4758-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0391] The 60th target gene is the hsa-miR-3679-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0392] The 61st target gene is the hsa-miR-3184-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0393] The 62nd target gene is the hsa-miR-6125 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0394] The 63rd target gene is the hsa-miR-6721-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0395] The 64th target gene is the hsa-miR-6791-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0396] The 65th target gene is the hsa-miR-3185 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0397] The 66th target gene is the hsa-miR-1260a gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0398] The 67th target gene is the hsa-miR-3197 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0399] The 68th target gene is the hsa-miR-6845-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0400] The 69th target gene is the hsa-miR-6887-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0401] The 70th target gene is the hsa-miR-6738-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0402] The 71st target gene is the hsa-miR-6872-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0403] The 72nd target gene is the hsa-miR-4497 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0404] The 73rd target gene is the hsa-miR-1229-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0405] The 74th target gene is the hsa-miR-6820-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0406] The 75th target gene is the hsa-miR-6777-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0407] The 76th target gene is the hsa-miR-3917 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0408] The 77th target gene is the hsa-miR-5787 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0409] The 78th target gene is the hsa-miR-4286 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0410] The 79th target gene is the hsa-miR-6877-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0411] The 80th target gene is the hsa-miR-1225-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0412] The 81st target gene is the hsa-miR-6088 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0413] The 82nd target gene is the hsa-miR-6800-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0414] The 83rd target gene is the hsa-miR-1246 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0415] The 84th target gene is the hsa-miR-4467 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0416] The 85th target gene is the hsa-miR-4419b gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0417] The 86th target gene is the hsa-miR-1914-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0418] The 87th target gene is the hsa-miR-4632-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0419] The 88th target gene is the hsa-miR-1915-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0420] The 89th target gene is the hsa-miR-3940-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0421] The 90th target gene is the hsa-miR-1185-2-3p gene and its homologs , their transcription products, or their mutants or derivatives. However, there are no known reports that changes in the expression of its transcripts can be a marker for liver cancer. stomach.
[0422] The 91st target gene is the hsa-miR-6746-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0423] The 92nd target gene is the hsa-miR-5001-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0424] The 93rd target gene is the hsa-miR-1228-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0425] The 94th target gene is the hsa-miR-5572 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0426] The 95th target gene is the hsa-miR-4327 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0427] The 96th target gene is the hsa-miR-4638-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0428] The 97th target gene is the hsa-miR-6799-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0429] The 98th target gene is the hsa-miR-6861-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0430] The 99th target gene is the hsa-miR-6727-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0431] The 100th target gene is the hsa-miR-4513 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0432] The 101st target gene is the hsa-miR-6805-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0433] The 102nd target gene is the hsa-miR-6808-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0434] The 103rd target gene is the hsa-miR-4449 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0435] The 104th target gene is the hsa-miR-1199-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0436] The 105th target gene is the hsa-miR-1275 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0437] The 106th target gene is the hsa-miR-4792 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0438] The 107th target gene is the hsa-miR-4443 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0439] The 108th target gene is the hsa-miR-6891-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0440] The 109th target gene is the hsa-miR-6826-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0441] The 110th target gene is the hsa-miR-6807-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0442] The 111th target gene is the hsa-miR-7150 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0443] The 112th target gene is the hsa-miR-4534 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0444] The 113th target gene is the hsa-miR-4476 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0445] The 114th target gene is the hsa-miR-4649-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0446] The 115th target gene is the hsa-miR-4525 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0447] The 116th target gene is the hsa-miR-1915-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0448] The 117th target gene is the hsa-miR-4516 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0449] The 118th target gene is the hsa-miR-4417 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0450] The 119th target gene is the hsa-miR-642b-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0451] The 120th target gene is the hsa-miR-3141 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0452] The 121st target gene is the hsa-miR-5100 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0453] The 122nd target gene is the hsa-miR-6848-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0454] The 123rd target gene is the hsa-miR-4739 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0455] The 124th target gene is the hsa-miR-4459 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0456] The 125th target gene is the hsa-miR-1237-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0457] The 126th target gene is the hsa-miR-296-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0458] The 127th target gene is the hsa-miR-4665-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0459] The 128th target gene is the hsa-miR-6786-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0460] The 129th target gene is the hsa-miR-4258 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0461] The 130th target gene is the hsa-miR-6510-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0462] The 131st target gene is the hsa-miR-1343-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0463] The 132nd target gene is the hsa-miR-1247-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0464] The 133rd target gene is the hsa-miR-6805-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0465] The 134th target gene is the hsa-miR-4492 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0466] The 135th target gene is the hsa-miR-1469 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0467] The 136th target gene is the hsa-miR-1268b gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0468] The 137th target gene is the hsa-miR-6858-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0469] The 138th target gene is the hsa-miR-3937 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0470] The 139th target gene is the hsa-miR-939-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0471] The 140th target gene is the hsa-miR-3656 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0472] The 141st target gene is the hsa-miR-744-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0473] The 142nd target gene is the hsa-miR-4687-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0474] The 143rd target gene is the hsa-miR-4763-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0475] The 144th target gene is the hsa-miR-3620-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0476] The 145th target gene is the hsa-miR-3195 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0477] The 146th target gene is the hsa-miR-6842-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0478] The 147th target gene is the hsa-miR-4707-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0479] The 148th target gene is the hsa-miR-642a-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0480] The 149th target gene is the hsa-miR-7113-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0481] The 150th target gene is the hsa-miR-4728-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0482] The 151st target gene is the hsa-miR-5195-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0483] The 152nd target gene is the hsa-miR-1185-1-3p gene and its homologs The gene is a member of the family of nucleotide sequences, or a transcription product thereof, or a variant or derivative thereof. There are no known reports that alterations in the expression of its transcripts can be markers for liver cancer. do not have.
[0484] The 153rd target gene is the hsa-miR-6774-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0485] The 154th target gene is the hsa-miR-8059 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0486] The 155th target gene is the hsa-miR-3131 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0487] The 156th target gene is the hsa-miR-7847-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0488] The 157th target gene is the hsa-miR-4463 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0489] The 158th target gene is the hsa-miR-128-2-5p gene and its homologs. , their transcription products, or their mutants or derivatives. However, there are no known reports that changes in the expression of its transcripts can be a marker for liver cancer. stomach.
[0490] The 159th target gene is the hsa-miR-4508 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0491] The 160th target gene is the hsa-miR-6806-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0492] The 161st target gene is the hsa-miR-7111-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0493] The 162nd target gene is the hsa-miR-6782-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0494] The 163rd target gene is the hsa-miR-4734 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0495] The 164th target gene is the hsa-miR-3162-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0496] The 165th target gene is the hsa-miR-887-3p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0497] The 166th target gene is the hsa-miR-6752-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0498] The 167th target gene is the hsa-miR-6724-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0499] The 168th target gene is the hsa-miR-23b-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Patent Document 2 and Patent Document 3).
[0500] The 169th target gene is the hsa-miR-23a-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 2).
[0501] The 170th target gene is the hsa-miR-625-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 4).
[0502] The 171st target gene is the hsa-miR-1228-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0503] The 172nd target gene is the hsa-miR-614 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. It has been reported that changes in the expression of the product can be a marker for liver cancer (Patent Document 2).
[0504] The 173rd target gene is the hsa-miR-1913 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. It has been reported that changes in the expression of transcripts can be a marker for liver cancer (Patent Document Reference 4).
[0505] The 174th target gene is the hsa-miR-92a-2-5p gene and its homologs , their transcription products, or their mutants or derivatives. It has been reported that changes in the expression of its transcripts can be a marker for liver cancer. (Patent Document 1).
[0506] The 175th target gene is the hsa-miR-187-5p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 5).
[0507] The 176th target gene is the hsa-miR-16-5p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. It has been reported that changes in the expression of transcripts can be a marker for liver cancer (Patent Reference 4 and Patent Document 5).
[0508] The 177th target gene is the hsa-miR-92b-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 1).
[0509] The 178th target gene is the hsa-miR-150-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 2).
[0510] The 179th target gene is the hsa-miR-564 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. It has been reported that changes in the expression of the product can be a marker for liver cancer (Patent Document 2).
[0511] The 180th target gene is the hsa-miR-125a-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. It has been reported that changes in the expression of this transcript can be a marker for liver cancer ( Patent document 3).
[0512] The 181st target gene is the hsa-miR-92b-5p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Permitted document 1).
[0513] The 182nd target gene is the hsa-miR-92a-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Patent Document 1, Patent Document 4 and Patent Document 5).
[0514] The 183rd target gene is the hsa-miR-663a gene, its homologs, and their The gene or its transcription product, or its variant or derivative. It has been reported that changes in the expression of transcripts can be a marker for liver cancer (Patent Document Reference 4).
[0515] The 184th target gene is the hsa-miR-4688 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0516] The 185th target gene is the hsa-miR-4648 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0517] The 186th target gene is the hsa-miR-6085 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0518] The 187th target gene is the hsa-miR-6126 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0519] The 188th target gene is the hsa-miR-6880-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0520] The 189th target gene is the hsa-miR-328-5p gene, its homologs, and These are transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0521] The 190th target gene is the hsa-miR-6768-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0522] The 191st target gene is the hsa-miR-3180 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0523] The 192nd target gene is the hsa-miR-6087 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0524] The 193rd target gene is the hsa-miR-1273g-3p gene and its homologs , their transcription products, or their mutants or derivatives. However, there are no known reports that changes in the expression of its transcripts can be a marker for liver cancer. stomach.
[0525] The 194th target gene is the hsa-miR-1225-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0526] The 195th target gene is the hsa-miR-3196 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0527] The 196th target gene is the hsa-miR-4695-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0528] The 197th target gene is the hsa-miR-6732-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0529] The 198th target gene is the hsa-miR-638 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0530] The 199th target gene is the hsa-miR-6813-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0531] The 200th target gene is the hsa-miR-665 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0532] The 201st target gene is the hsa-miR-486-3p gene, its homologs, and These are transcription products, or their variants or derivatives. It has been reported that changes in the expression of transcriptional products of the Patent Document 2 and Patent Document 3).
[0533] The 202nd target gene is the hsa-miR-4466 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0534] The 203rd target gene is the hsa-miR-30c-1-3p gene and its homologs , their transcription products, or their mutants or derivatives. It has been reported that changes in the expression of its transcripts can be a marker for liver cancer. (Patent Documents 3 and 5).
[0535] The 204th target gene is the hsa-miR-3621 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0536] The 205th target gene is the hsa-miR-6743-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0537] The 206th target gene is the hsa-miR-4298 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0538] The 207th target gene is the hsa-miR-4741 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0539] The 208th target gene is the hsa-miR-3619-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0540] The 209th target gene is the hsa-miR-6824-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0541] The 210th target gene is the hsa-miR-5698 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0542] The 211th target gene is the hsa-miR-371a-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0543] The 212th target gene is the hsa-miR-4488 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0544] The 213th target gene is the hsa-miR-1233-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0545] The 214th target gene is the hsa-miR-4723-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0546] The 215th target gene is the hsa-miR-24-3p gene, its homologs, and The gene is a transcription product of the gene, or a variant or derivative thereof. It has been reported that changes in the expression of transcripts can be a marker for liver cancer (Patent Reference 2).
[0547] The 216th target gene is the hsa-miR-1238-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0548] The 217th target gene is the hsa-miR-4442 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0549] The 218th target gene is the hsa-miR-3928-3p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0550] The 219th target gene is the hsa-miR-6716-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0551] The 220th target gene is the hsa-miR-6089 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0552] The 221st target gene is the hsa-miR-6124 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0553] The 222nd target gene is the hsa-miR-6778-5p gene, its homologs, The gene is a transcription product thereof, or a variant or derivative thereof. There are no known reports that altered expression of this transcript could be a marker for liver cancer. .
[0554] The 223rd target gene is the hsa-miR-557 gene, its homologs, and their The gene or its transcription product, or a variant or derivative thereof. It has been reported that changes in the expression of the product can be a marker for liver cancer (Patent Document 2).
[0555] The 224th target gene is the hsa-miR-6090 gene, its homologs, and their The gene or its transcription product, or its variant or derivative. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0556] The 225th target gene is the hsa-miR-6757-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0557] The 226th target gene is the hsa-miR-4448 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0558] The 227th target gene is the hsa-miR-671-5p gene, its homologs, and These are transcription products, or variants or derivatives thereof. There are no known reports that altered transcript expression can be a marker for liver cancer.
[0559] The 228th target gene is the hsa-miR-3178 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0560] The 229th target gene is the hsa-miR-4725-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0561] The 230th target gene is the hsa-miR-940 gene, its homologs, and their The gene or its transcript, or a variant or derivative thereof. There are no known reports that altered expression of these substances can be markers for liver cancer.
[0562] The 231st target gene is the hsa-miR-6789-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0563] The 232nd target gene is the hsa-miR-4484 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0564] The 233rd target gene is the hsa-miR-4634 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0565] The 234th target gene is the hsa-miR-4745-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0566] The 235th target gene is the hsa-miR-4730 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0567] The 236th target gene is the hsa-miR-6803-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0568] The 237th target gene is the hsa-miR-6798-5p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0569] The 238th target gene is the hsa-miR-3648 gene, its homologs, and their or their variants or derivatives. There are no known reports suggesting that changes in expression of these products could be markers for liver cancer.
[0570] The 239th target gene is the hsa-miR-4783-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0571] The 240th target gene is the hsa-miR-6836-3p gene, its homologs, The genes or their transcription products, or their variants or derivatives. There are no known reports that altered expression of this transcript could be a marker for liver cancer.
[0572] 2. Nucleic acid probes or primers for detecting liver cancer In the present invention, a nucleic acid capable of specifically binding to the target nucleic acid as the liver cancer marker is The acid can be used as a nucleic acid, such as a nucleic acid probe or primer, for detecting or diagnosing liver cancer. It can be used as such.
[0573] In the present invention, the use for detecting or diagnosing liver cancer Possible nucleic acid probes or primers include target nucleic acids such as those listed above as liver cancer markers, e.g. For example, human-derived hsa-miR-1343-3p, hsa-miR-6726-5p, and hs a-miR-6515-3p, hsa-miR-4651, hsa-miR-4257, hsa-miR-3188, hsa-miR-6131, hsa-miR-6766-3 p, hsa-miR-7641, hsa-miR-1249, hsa-miR-3679 -3p, hsa-miR-6787-5p, hsa-miR-4454, hsa-miR -3135b, hsa-miR-6765-3p, hsa-miR-7975, hsa- miR-204-3p, hsa-miR-7977, hsa-miR-7110-5p, hsa-miR-6717-5p, hsa-miR-6870-5p, hsa-miR- 663b, hsa-miR-6875-5p, hsa-miR-8072, hsa-mi R-6816-5p, hsa-miR-4281, hsa-miR-6729-5p, h sa-miR-8069, hsa-miR-4706, hsa-miR-7108-5p 、hsa-miR-4433b-3p、hsa-miR-6893-5p、hsa-mi R-6857-5p、hsa-miR-1227-5p、hsa-miR-6741-5 p, hsa-miR-451a, hsa-miR-8063, hsa-miR-3622 a-5p、hsa-miR-615-5p、hsa-miR-128-1-5p、hsa -miR-6825-5p、hsa-miR-1260b、hsa-miR-4433- 3p、hsa-miR-4665-5p、hsa-miR-7845-5p、hsa-m iR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765- 5p、hsa-miR-296-5p、hsa-miR-3675-3p、hsa-mi R-6781-5p、hsa-miR-423-5p、hsa-miR-3663-3p hsa-miR-6784-5p hsa-miR-6749-5p hsa-miR -1231、hsa-miR-4746-3p、hsa-miR-6780b-5p、h sa-miR-4758-5p、hsa-miR-3679-5p、hsa-miR-3 184-5p、hsa-miR-6125、hsa-miR-6721-5p、hsa- miR-6791-5p, hsa-miR-3185, hsa-miR-1260a, h sa-miR-3197, hsa-miR-6845-5p, hsa-miR-6887 -5p、hsa-miR-6738-5p、hsa-miR-6872-3p、hsa- miR-4497, hsa-miR-1229-5p, hsa-miR-6820-5p hsa-miR-6777-5p hsa-miR-3917 hsa-miR-57 87、hsa-miR-4286、hsa-miR-6877-5p、hsa-miR- 1225-3p, hsa-miR-6088, hsa-miR-6800-5p, hsa -miR-1246、hsa-miR-4467、hsa-miR-4419b、hsa -miR-1914-3p、hsa-miR-4632-5p、hsa-miR-191 5-5p、hsa-miR-3940-5p、hsa-miR-1185-2-3p、h sa-miR-6746-5p, hsa-miR-5001-5p, hsa-miR-1 228-5p、hsa-miR-5572、hsa-miR-4327、hsa-miR -4638-5p、hsa-miR-6799-5p、hsa-miR-6861-5p hsa-miR-6727-5p hsa-miR-4513 hsa-miR-68 05-3p、hsa-miR-6808-5p、hsa-miR-4449、hsa-m iR-1199-5p, hsa-miR-1275, hsa-miR-4792, hsa -miR-4443、hsa-miR-6891-5p、hsa-miR-6826-5 p, hsa-miR-6807-5p, hsa-miR-7150, hsa-miR-4 534、hsa-miR-4476、hsa-miR-4649-5p、hsa-miR -4525、hsa-miR-1915-3p、hsa-miR-4516、hsa-m iR-4417, hsa-miR-642b-3p, hsa-miR-3141, hsa -miR-5100、hsa-miR-6848-5p、hsa-miR-4739、h sa-miR-4459、hsa-miR-1237-5p、hsa-miR-296- 3p、hsa-miR-4665-3p、hsa-miR-6786-5p、hsa-m iR-4258, hsa-miR-6510-5p, hsa-miR-1343-5p hsa-miR-1247-3p、hsa-miR-6805-5p、hsa-miR- 4492、hsa-miR-1469、hsa-miR-1268b、hsa-miR- 6858-5p、hsa-miR-3937、hsa-miR-939-5p、hsa- miR-3656, hsa-miR-744-5p, hsa-miR-4687-3p hsa-miR-4763-3p、hsa-miR-3620-5p、hsa-miR- 3195、hsa-miR-6842-5p、hsa-miR-4707-5p、hsa -miR-642a-3p、hsa-miR-7113-3p、hsa-miR-472 8-5p、hsa-miR-5195-3p、hsa-miR-1185-1-3p、h sa-miR-6774-5p, hsa-miR-8059, hsa-miR-3131 hsa-miR-7847-3p hsa-miR-4463 hsa-miR-12 8-2-5p、hsa-miR-4508、hsa-miR-6806-5p、hsa- miR-7111-5p, hsa-miR-6782-5p, hsa-miR-4734 hsa-miR-3162-5p hsa-miR-887-3p hsa-miR- 6752-5p, hsa-miR-6724-5p, hsa-miR-6757-5p hsa-miR-4448, hsa-miR-671-5p, hsa-miR-3178 hsa-miR-4725-3p hsa-miR-940 hsa-miR-678 9-5p, hsa-miR-4484, hsa-miR-4634, hsa-miR-4 745-5p, hsa-miR-4730, hsa-miR-6803-5p, hsa- miR-6798-5p, hsa-miR-3648, hsa-miR-4783-3p , or hsa-miR-6836-3p, or a combination thereof, or the same and the like, including but not limited to, a family, a transcription product thereof, a variant or derivative thereof, and optionally Can be combined, hsa-miR-23b-3p, hsa-miR-23a- 3p, hsa-miR-625-3p, hsa-miR-1228-3p, hsa-mi R-614, hsa-miR-1913, hsa-miR-92a-2-5p, hsa- miR-187-5p, hsa-miR-16-5p, hsa-miR-92b-3p, hsa-miR-150-3p, hsa-miR-564, hsa-miR-125a- 3p, hsa-miR-92b-5p, hsa-miR-92a-3p, or hsa miR-663a, or a combination thereof, or a homolog thereof, or a transcript thereof , variants or derivatives thereof, and optionally combinations thereof. hsa-miR-4688, hsa-miR-4648, hsa-miR-6085 , hsa-miR-6126, hsa-miR-6880-5p, hsa-miR-32 8-5p, hsa-miR-6768-5p, hsa-miR-3180, hsa-mi R-6087, hsa-miR-1273g-3p, hsa-miR-1225-5p, hsa-miR-3196, hsa-miR-4695-5p, hsa-miR-673 2-5p, hsa-miR-638, hsa-miR-6813-5p, hsa-miR -665, hsa-miR-486-3p, hsa-miR-4466, hsa-miR -30c-1-3p, hsa-miR-3621, hsa-miR-6743-5p, h sa-miR-4298, hsa-miR-4741, hsa-miR-3619-3p , hsa-miR-6824-5p, hsa-miR-5698, hsa-miR-37 1a-5p, hsa-miR-4488, hsa-miR-1233-5p, hsa-m iR-4723-5p, hsa-miR-24-3p, hsa-miR-1238-5p , hsa-miR-4442, hsa-miR-3928-3p, hsa-miR-67 16-5p, hsa-miR-6089, hsa-miR-6124, hsa-miR- 6778-5p, hsa-miR-557, or hsa-miR-6090, or combinations thereof, or their homologs, transcription products, variants or derivatives thereof Allows the presence, expression level or abundance of conductors to be measured qualitatively and / or quantitatively. .
[0574] The target nucleic acid is a nucleic acid that is expressed by a nucleic acid sequence ... Depending on the type of gene, the expression levels of some genes may increase or decrease (see below). (These are referred to as "increase / decrease"). Therefore, the nucleic acid of the present invention can be used to detect liver cancer in patients suspected of having liver cancer. The expression level of the target nucleic acid is measured in body fluids derived from a subject (e.g., a human) and body fluids derived from a healthy subject. The results can be used to detect liver cancer by comparing the results of the measurements.
[0575] Nucleic acid probes or primers that can be used in the present invention are those represented by SEQ ID NOs: 1 to 167 and 714 to 716. A polynucleotide consisting of a nucleotide sequence represented by at least one of 729 and capable of specifically binding thereto An nucleic acid probe, or a primer for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 1 to 167 and 714 to 729 is provided.
[0576] The nucleic acid probe or primer usable in the present invention may further include an nucleic acid probe capable of specifically binding to a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 168 to 183, or a primer for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 168 to 183 is provided. The nucleic acid probe or primer usable in the present invention may further include an nucleic acid
[0577] probe capable of specifically binding to a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 184 to 224, or a primer for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 184 to 224 is provided. The nucleic acid probe or primer usable in the present invention may further include an nucleic acid probe capable of specifically binding to a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 184 to 224, or a primer for amplifying a polynucleotide consisting of a nucleotide sequence represented by at least one of SEQ ID NOs: 184 to 224
[0578] Specifically, the above nucleic acid probe or primer includes a polynucleotide group containing a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence in which u is t in the nucleotide sequence, and a complementary polynucleotide group thereof, a polynucleotide group that hybridizes with DNA consisting of a nucleotide sequence complementary to the nucleotide sequence under stringent conditions (described below) and a complementary polynucleotide group thereof, and a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the nucleotide sequence of these polynucleotide groups is provided. Specifically, the above nucleic acid probe or primer includes a polynucleotide group containing a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence in which u is t in the nucleotide sequence, and a complementary polynucleotide group thereof, a polynucleotide group that hybridizes with DNA consisting of a nucleotide sequence complementary to the nucleotide sequence under stringent conditions (described below) and a complementary polynucleotide group thereof, and a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the nucleotide sequence of these polynucleotide groups Specifically, the above nucleic acid probe or primer includes a polynucleotide group containing a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence in which u is t in the nucleotide sequence, and a complementary polynucleotide group thereof, a polynucleotide group that hybridizes with DNA consisting of a nucleotide sequence complementary to the nucleotide sequence under stringent conditions (described below) and a complementary polynucleotide group thereof, and a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the nucleotide sequence of these polynucleotide groups Specifically, the above nucleic acid probe or primer includes a polynucleotide group containing a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence in which u is t in the nucleotide sequence, and a complementary polynucleotide group thereof, a polynucleotide group that hybridizes with DNA consisting of a nucleotide sequence complementary to the nucleotide sequence under stringent conditions (described below) and a complementary polynucleotide group thereof, and a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the nucleotide sequence of these polynucleotide groups Specifically, the above nucleic acid probe or primer includes a polynucleotide group containing a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 765, or a nucleotide sequence in which u is t in the nucleotide sequence, and a complementary polynucleotide group thereof, a polynucleotide group that hybridizes with DNA consisting of a nucleotide sequence complementary to the nucleotide sequence under stringent conditions (described below) and a complementary polynucleotide group thereof, and a polynucleotide group containing 15 or more, preferably 17 or more consecutive bases in the nucleotide sequence of these polynucleotide groups is provided. The method comprises the steps of: preparing a nucleic acid probe and a primer for detecting the liver cancer marker, which is a target nucleic acid; It can be used as a
[0579] More specifically, examples of nucleic acid probes or primers that can be used in the present invention include the following: One or more polynucleotides selected from the group consisting of polynucleotides (a) to (e). is.
[0580] (a) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a polynucleotide consisting of a base sequence in which u is replaced with t, or a variant thereof; Its derivatives are fragments thereof containing 15 or more consecutive bases, (b) a polypeptide containing a base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729; nucleotide, (c) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or A polynucleotide consisting of a base sequence complementary to the base sequence in which u is t a nucleotide sequence of 15 or more consecutive bases, a variant thereof, a derivative thereof, or a fragment thereof, (d) a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or A polynucleotide containing a base sequence complementary to the base sequence in which u is t Do, as well as (e) A polynucleotide that binds to any one of the polynucleotides (a) to (d) under stringent conditions. Hybridizing polynucleotide.
[0581] The nucleic acid probe or primer that can be used in the present invention further includes the above-mentioned polynucleotide ( In addition to at least one polynucleotide selected from the group consisting of a) to (e), A polynucleotide selected from the group consisting of the polynucleotides (f) to (j) below: It can contain (f) a base sequence represented by any one of SEQ ID NOs: 168 to 183 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (g) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 168 to 183; (h) a base sequence represented by any one of SEQ ID NOs: 168 to 183, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (i) a base sequence represented by any one of SEQ ID NOs: 168 to 183, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (j) A method for detecting a polynucleotide that is hybridized with any one of the polynucleotides (f) to (i) under stringent conditions. Hybridizing polynucleotide.
[0582] The nucleic acid probe or primer that can be used in the present invention further includes the above-mentioned polynucleotide ( In addition to at least one polynucleotide selected from the group consisting of a) to (j), A polynucleotide selected from the group consisting of the polynucleotides (k) to (o) below: It can contain
[0583] (k) a base sequence represented by any one of SEQ ID NOs: 184 to 224 or the base sequence a polynucleotide consisting of a base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 5 or more consecutive bases; (l) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 184 to 224; (m) a base sequence represented by any one of SEQ ID NOs: 184 to 224, or the base sequence a polynucleotide consisting of a base sequence complementary to the base sequence in which u is t, and a variant thereof a fragment thereof containing 15 or more consecutive bases, (n) a base sequence represented by any one of SEQ ID NOs: 184 to 224, or the base sequence a polynucleotide comprising a base sequence complementary to the base sequence in which u is t; and (o) a polynucleotide that binds to any one of the polynucleotides (k) to (n) under stringent conditions; Hybridizing polynucleotide.
[0584] In the above polynucleotide, "a fragment containing 15 or more consecutive bases" means each polynucleotide. In a base sequence of a polynucleotide, for example, 15 consecutive bases or less than the total number of bases in the sequence, It may contain a range of base numbers, such as 7 to less than the total number of bases in the sequence, or 19 to less than the total number of bases in the sequence. The present invention can be implemented in the following ways, but is not limited to these.
[0585] The polynucleotides or fragments thereof used in the present invention may be DNA. RNA may also be used.
[0586] The above polynucleotides that can be used in the present invention can be synthesized by DNA recombination techniques, PCR methods, DNA / It can be prepared using common techniques such as methods using an automatic RNA synthesizer.
[0587] The DNA recombination technique and the PCR method are described, for example, in Ausubel et al., Current Proc. otocols in Molecular Biology, John Wille y & Sons, US (1993); Sambrook et al., Molecula r Cloning A Laboratory Manual, Cold Spr. Harbor Laboratory Press, US (1989), etc. The techniques described in can be used.
[0588] Human-derived hsa-miR-134 represented by SEQ ID NOs: 1 to 224 and 714 to 729 3-3p, hsa-miR-6726-5p, hsa-miR-6515-3p, hsa -miR-4651, hsa-miR-4257, hsa-miR-3188, hsa- miR-6131, hsa-miR-6766-3p, hsa-miR-7641, hs a-miR-1249, hsa-miR-3679-3p, hsa-miR-6787- 5p, hsa-miR-4454, hsa-miR-3135b, hsa-miR-67 65-3p, hsa-miR-7975, hsa-miR-204-3p, hsa-mi R-7977, hsa-miR-7110-5p, hsa-miR-6717-5p, h sa-miR-6870-5p, hsa-miR-663b, hsa-miR-6875 -5p, hsa-miR-8072, hsa-miR-6816-5p, hsa-miR -4281, hsa-miR-6729-5p, hsa-miR-8069, hsa-m iR-4706, hsa-miR-7108-5p, hsa-miR-4433b-3p , hsa-miR-6893-5p, hsa-miR-6857-5p, hsa-miR -1227-5p, hsa-miR-6741-5p, hsa-miR-451a, hs a-miR-8063, hsa-miR-3622a-5p, hsa-miR-615- 5p、hsa-miR-128-1-5p、hsa-miR-6825-5p、hsa- miR-1260b, hsa-miR-4433-3p, hsa-miR-4665-5 p、hsa-miR-7845-5p、hsa-miR-1908-5p、hsa-mi R-6840-3p、hsa-miR-6765-5p、hsa-miR-296-5p hsa-miR-3675-3p hsa-miR-6781-5p hsa-miR -423-5p、hsa-miR-3663-3p、hsa-miR-6784-5p、 hsa-miR-6749-5p, hsa-miR-1231, hsa-miR-474 6-3p、hsa-miR-6780b-5p、hsa-miR-4758-5p、hs a-miR-3679-5p, hsa-miR-3184-5p, hsa-miR-61 25、hsa-miR-6721-5p、hsa-miR-6791-5p、hsa-m iR-3185、hsa-miR-1260a、hsa-miR-3197、hsa-m iR-6845-5p, hsa-miR-6887-5p, hsa-miR-6738- 5p、hsa-miR-6872-3p、hsa-miR-4497、hsa-miR- 1229-5p、hsa-miR-6820-5p、hsa-miR-6777-5p、 hsa-miR-3917、hsa-miR-5787、hsa-miR-4286、h sa-miR-6877-5p, hsa-miR-1225-3p, hsa-miR-6 088、hsa-miR-6800-5p、hsa-miR-1246、hsa-miR -4467、hsa-miR-4419b、hsa-miR-1914-3p、hsa- miR-4632-5p, hsa-miR-1915-5p, hsa-miR-3940 -5p、hsa-miR-1185-2-3p、hsa-miR-6746-5p、hs a-miR-5001-5p, hsa-miR-1228-5p, hsa-miR-55 72、hsa-miR-4327、hsa-miR-4638-5p、hsa-miR- 6799-5p、hsa-miR-6861-5p、hsa-miR-6727-5p、 hsa-miR-4513, hsa-miR-6805-3p, hsa-miR-680 8-5p、hsa-miR-4449、hsa-miR-1199-5p、hsa-mi R-1275, hsa-miR-4792, hsa-miR-4443, hsa-miR -6891-5p、hsa-miR-6826-5p、hsa-miR-6807-5p hsa-miR-7150 hsa-miR-4534 hsa-miR-4476 hsa-miR-4649-5p, hsa-miR-4525, hsa-miR-191 5-3p、hsa-miR-4516、hsa-miR-4417、hsa-miR-6 42b-3p、hsa-miR-3141、hsa-miR-5100、hsa-miR -6848-5p、hsa-miR-4739、hsa-miR-4459、hsa-m iR-1237-5p, hsa-miR-296-3p, hsa-miR-4665-3 p、hsa-miR-6786-5p、hsa-miR-4258、hsa-miR-6 510-5p、hsa-miR-1343-5p、hsa-miR-1247-3p、h sa-miR-6805-5p, hsa-miR-4492, hsa-miR-1469 hsa-miR-1268b hsa-miR-6858-5p hsa-miR-3 937、hsa-miR-939-5p、hsa-miR-3656、hsa-miR- 744-5p、hsa-miR-4687-3p、hsa-miR-4763-3p、h sa-miR-3620-5p, hsa-miR-3195, hsa-miR-6842 -5p、hsa-miR-4707-5p、hsa-miR-642a-3p、hsa- miR-7113-3p, hsa-miR-4728-5p, hsa-miR-5195 -3p、hsa-miR-1185-1-3p、hsa-miR-6774-5p、hs a-miR-8059, hsa-miR-3131, hsa-miR-7847-3p hsa-miR-4463, hsa-miR-128-2-5p, hsa-miR-45 08、hsa-miR-6806-5p、hsa-miR-7111-5p、hsa-m iR-6782-5p, hsa-miR-4734, hsa-miR-3162-5p hsa-miR-887-3p, hsa-miR-6752-5p, hsa-miR-6 724-5p、hsa-miR-6757-5p、hsa-miR-4448、hsa- miR-671-5p, hsa-miR-3178, hsa-miR-4725-3p hsa-miR-940, hsa-miR-6789-5p, hsa-miR-4484 hsa-miR-4634 hsa-miR-4745-5p hsa-miR-47 30、hsa-miR-6803-5p、hsa-miR-6798-5p、hsa-m iR-3648、hsa-miR-4783-3p、hsa-miR-6836-3p、 hsa-miR-23b-3p、hsa-miR-23a-3p、hsa-miR-62 5-3p、hsa-miR-1228-3p、hsa-miR-614、hsa-miR -1913、hsa-miR-92a-2-5p、hsa-miR-187-5p、hs a-miR-16-5p, hsa-miR-92b-3p, hsa-miR-150-3 p、hsa-miR-564、hsa-miR-125a-3p、hsa-miR-92 b-5p、hsa-miR-92a-3p、hsa-miR-663a、hsa-miR -4688、hsa-miR-4648、hsa-miR-6085、hsa-miR- 6126、hsa-miR-6880-5p、hsa-miR-328-5p、hsa- miR-6768-5p, hsa-miR-3180, hsa-miR-6087, hs a-miR-1273g-3p, hsa-miR-1225-5p, hsa-miR-3 196、hsa-miR-4695-5p、hsa-miR-6732-5p、hsa- miR-638, hsa-miR-6813-5p, hsa-miR-665, hsa- miR-486-3p, hsa-miR-4466, hsa-miR-30c-1-3p hsa-miR-3621 hsa-miR-6743-5p hsa-miR-42 98、hsa-miR-4741、hsa-miR-3619-3p、hsa-miR- 6824-5p、hsa-miR-5698、hsa-miR-371a-5p、hsa -miR-4488、hsa-miR-1233-5p、hsa-miR-4723-5 p、hsa-miR-24-3p、hsa-miR-1238-5p、hsa-miR- 4442、hsa-miR-3928-3p、hsa-miR-6716-5p、hsa -miR-6089、hsa-miR-6124、hsa-miR-6778-5p、h sa-miR-557 and hsa-miR-6090 are known, and as described above, their preparation Therefore, by cloning this gene, the present invention can be It is possible to prepare polynucleotides as nucleic acid probes or primers that can be used in Cut.
[0589] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. This synthesis is generally carried out using the phosphoramidite method, which The automated DNA synthesizer can automatically synthesize single-stranded DNA up to about 100 bases. For example, Polygen, ABI, Applied BioSystems, etc. It is commercially available.
[0590] Alternatively, the polynucleotides of the present invention can be produced by cDNA cloning techniques. cDNA cloning technology is also possible, for example, microRNA cloning You can use Kit Wako etc.
[0591] Here, the nucleic acid sequence is a sequence represented by any one of SEQ ID NOs: 1 to 224 and 714 to 729. The sequences of the nucleic acid probes and primers for detecting the polynucleotides Or, it does not exist in vivo as a precursor thereof. For example, SEQ ID NO: 1 and SEQ ID NO: 13 The base sequence represented by SEQ ID NO: 1 is generated from the precursor represented by SEQ ID NO: 225. The peptide has a hairpin-like structure as shown in FIG. 1 and is represented by SEQ ID NO: 1 and SEQ ID NO: 131. The base sequences to be used have mismatch sequences. The completely complementary base sequence to the base sequence represented by No. 131 is naturally produced in vivo. Similarly, the sequences represented by any of SEQ ID NOs: 1 to 224 and 714 to 729 will not be used. The nucleic acid probes and primers used to detect base sequences are artificial salts that do not exist in living organisms. It will have a base sequence.
[0592] 3. Liver cancer detection kit or device The present invention also relates to a method for measuring a target nucleic acid that is a liver cancer marker, comprising the steps of: Polynucleotides that can be used as nucleic acid probes or primers (including mutants, fragments, or a derivative thereof (hereinafter sometimes referred to as a detection polynucleotide). or a kit or device for detecting liver cancer comprising a plurality of the above components.
[0593] The target nucleic acid that is a liver cancer marker in the present invention is preferably selected from the following Group 1: To be: miR-1343-3p, miR-6726-5p, miR-6515-3p, miR -4651, miR-4257, miR-3188, miR-6131, miR-676 6-3p, miR-7641, miR-1249, miR-3679-3p, miR-6 787-5p, miR-4454, miR-3135b, miR-6765-3p, mi R-7975, miR-204-3p, miR-7977, miR-7110-5p, m iR-6717-5p, miR-6870-5p, miR-663b, miR-6875 -5p, miR-8072, miR-6816-5p, miR-4281, miR-67 29-5p, miR-8069, miR-4706, miR-7108-5p, miR- 4433b-3p, miR-6893-5p, miR-6857-5p, miR-122 7-5p, miR-6741-5p, miR-451a, miR-8063, miR-3 622a-5p, miR-615-5p, miR-128-1-5p, miR-6825 -5p, miR-1260b, miR-4433-3p, miR-4665-5p, mi R-7845-5p, miR-1908-5p, miR-6840-3p, miR-67 65-5p, miR-296-5p, miR-3675-3p, miR-6781-5p miR-423-5p miR-3663-3p miR-6784-5p miR- 6749-5p, miR-1231, miR-4746-3p, miR-6780b-5 p, miR-4758-5p, miR-3679-5p, miR-3184-5p, mi R-6125, miR-6721-5p, miR-6791-5p, miR-3185 miR-1260a, miR-3197, miR-6845-5p, miR-6887- 5p、miR-6738-5p、miR-6872-3p、miR-4497、miR- 1229-5p, miR-6820-5p, miR-6777-5p, miR-3917 miR-5787 miR-4286 miR-6877-5p miR-1225- 3p, miR-6088, miR-6800-5p, miR-1246, miR-446 7、miR-4419b、miR-1914-3p、miR-4632-5p、miR- 1915-5p, miR-3940-5p, miR-1185-2-3p, miR-67 46-5p, miR-5001-5p, miR-1228-5p, miR-5572, m iR-4327, miR-4638-5p, miR-6799-5p, miR-6861 -5p, miR-6727-5p, miR-4513, miR-6805-3p, miR -6808-5p, miR-4449, miR-1199-5p, miR-1275, m iR-4792, miR-4443, miR-6891-5p, miR-6826-5p miR-6807-5p miR-7150 miR-4534 miR-4476 miR-4649-5p, miR-4525, miR-1915-3p, miR-451 6, miR-4417, miR-642b-3p, miR-3141, miR-5100 miR-6848-5p miR-4739 miR-4459 miR-1237- 5p, miR-296-3p, miR-4665-3p, miR-6786-5p, mi R-4258, miR-6510-5p, miR-1343-5p, miR-1247- 3p, miR-6805-5p, miR-4492, miR-1469, miR-126 8b, miR-6858-5p, miR-3937, miR-939-5p, miR-3 656, miR-744-5p, miR-4687-3p, miR-4763-3p, m iR-3620-5p, miR-3195, miR-6842-5p, miR-4707 -5p、miR-642a-3p、miR-7113-3p、miR-4728-5p、 miR-5195-3p, miR-1185-1-3p, miR-6774-5p, mi R-8059, miR-3131, miR-7847-3p, miR-4463, miR -128-2-5p、miR-4508、miR-6806-5p、miR-7111- 5p, miR-6782-5p, miR-4734, miR-3162-5p, miR- 887-3p, miR-6752-5p, miR-6724-5p, miR-6757- 5p, miR-4448, miR-671-5p, miR-3178, miR-4725 -3p, miR-940, miR-6789-5p, miR-4484, miR-463 4, miR-4745-5p, miR-4730, miR-6803-5p, miR-6 798-5p, miR-3648, miR-4783-3p and miR-6836-3p .
[0594] The additional target nucleic acid that may be used for measurement is preferably selected from the following group 2: : miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1 228-3p, miR-614, miR-1913, miR-92a-2-5p, miR -187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3 p and miR-663a.
[0595] The additional target nucleic acid that can be optionally further used for measurement is preferably selected from the following Group 3: Selected: miR-4688, miR-4648, miR-6085, miR-6126 , miR-6880-5p, miR-328-5p, miR-6768-5p, miR- 3180, miR-6087, miR-1273g-3p, miR-1225-5p, m iR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-42 98, miR-4741, miR-3619-3p, miR-6824-5p, miR- 5698, miR-371a-5p, miR-4488, miR-1233-5p, mi R-4723-5p, miR-24-3p, miR-1238-5p, miR-4442 , miR-3928-3p, miR-6716-5p, miR-6089, miR-61 24, miR-6778-5p, miR-557 and miR-6090.
[0596] The kit or device of the present invention specifically binds to the target nucleic acid, which is the liver cancer marker. A nucleic acid capable of synthesizing, preferably, the nucleic acid probe or primer described in 2 above, specifically, One or more polynucleotides selected from the polynucleotides described in item 2 or This includes mutants of the above.
[0597] Specifically, the kit or device of the present invention includes SEQ ID NOs: 1 to 167 and 714 to 729 or a base sequence in which u is t in the base sequence, a polynucleotide comprising (or consisting of) the complementary sequence thereof; Polynucleotides that hybridize with those polynucleotides under stringent conditions A hybridizing polynucleotide or 15 or more consecutive sequences of such polynucleotide sequences The nucleic acid sequence may include at least one or more mutants or fragments containing the same base.
[0598] The kit or device of the present invention further comprises a compound represented by any one of SEQ ID NOs: 168 to 183. A base sequence, or a base sequence in which u is t in the base sequence (or a polynucleotide comprising (or consisting of) its complementary sequence; Polynucleotides that hybridize under stringent conditions with these polynucleotides. nucleotides or variants containing 15 or more consecutive bases of their polynucleotide sequences or fragments thereof.
[0599] The kit or device of the present invention further comprises a compound represented by any one of SEQ ID NOs: 184 to 224. A base sequence, or a base sequence in which u is t in the base sequence (or a polynucleotide comprising (or consisting of) its complementary sequence; Polynucleotides that hybridize under stringent conditions with these polynucleotides. nucleotides or variants containing 15 or more consecutive bases of their polynucleotide sequences or fragments thereof.
[0600] The fragments that can be contained in the kit or device of the present invention include, for example, the following fragments (1) to (3): The polynucleotide is one or more, preferably two or more, selected from the group consisting of: (1) In a base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729 Polynucleotides containing 15 or more consecutive bases in the base sequence where u is t or its complementary sequence nucleotide. (2) A salt in which u is t in the base sequence represented by any one of SEQ ID NOs: 168 to 183 A polynucleotide containing 15 or more consecutive bases in the base sequence or its complementary sequence. (3) A salt in which u is t in the base sequence represented by any one of SEQ ID NOs: 184 to 224 A polynucleotide containing 15 or more consecutive bases in the base sequence or its complementary sequence.
[0601] In a preferred embodiment, the polynucleotide is selected from the group consisting of SEQ ID NOs: 1 to 167 and 714 to 7 29, or the base sequence in which u is t a polynucleotide consisting of the sequence, a polynucleotide consisting of the complementary sequence, a polynucleotide that hybridizes under stringent conditions with the It contains 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof. It is a mutant.
[0602] In a preferred embodiment, the polynucleotide is any one of SEQ ID NOs: 168 to 183. A base sequence represented by either of t...
Claims
1. A kit for detecting liver cancer, comprising a nucleic acid capable of specifically binding to a polynucleotide of miR-6088, a liver cancer marker.
2. The kit according to claim 1, wherein the nucleic acid is selected from the group consisting of polynucleotides or fragments thereof shown in (a) to (e) below: (a) (1) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (2) A polynucleotide or a fragment thereof comprising the polynucleotide or the fragment of (1) above, which contains a deletion, substitution, addition, or insertion of one or two bases. (3) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (1). (4) A polynucleotide or a fragment thereof according to any one of (1) to (3), which contains a modified nucleic acid and / or a modified nucleotide. (b) a polynucleotide comprising the base sequence represented by SEQ ID NO: 81, or a fragment thereof comprising 15 or more consecutive bases; (c) (5) A polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (6) A polynucleotide or a fragment thereof according to (5), which contains a deletion, substitution, addition, or insertion of one or two bases. (7) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (5). (8) A polynucleotide or a fragment thereof according to any one of (5) to (7), which contains a modified nucleic acid and / or a modified nucleotide. (d) a polynucleotide containing a base sequence complementary to the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; and (e) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d) or fragments thereof.
3. The kit includes miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p, miR-6717-5p, miR-6870-5p, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-4286, miR-6877-5p, miR-1225-3p, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p, which are another liver cancer marker.The group consisting of miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p, miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508, miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6724-5p, miR-6757-5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR-4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and miR-6836-3p; and / or, miR-23b-3p,miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16 -5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p, miR-663a, miR- 4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6 087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p , miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR The kit according to claim 1 or 2, further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
4. The kit according to claim 3, wherein the nucleic acid is selected from the group consisting of polynucleotides or fragments thereof shown in (f) to (j) below: (f) (9) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (10) A polynucleotide or a fragment thereof according to (9), which contains a deletion, substitution, addition, or insertion of one or two bases. (11) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (9). (12) A polynucleotide or a fragment thereof according to any one of (9) to (11), which contains a modified nucleic acid and / or a modified nucleotide. (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or a fragment thereof comprising 15 or more consecutive bases; (h) (13) A polynucleotide consisting of a base sequence complementary to any of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (14) A polynucleotide or a fragment thereof according to (13), which contains a deletion, substitution, addition, or insertion of one or two bases. (15) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (13). (16) A polynucleotide or a fragment thereof according to any one of (13) to (15), which contains a modified nucleic acid and / or a modified nucleotide. (i) a polynucleotide containing a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (j) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i) or fragments thereof.
5. A device for detecting liver cancer, comprising a nucleic acid capable of specifically binding to a polynucleotide of miR-6088, a liver cancer marker.
6. The device according to claim 5, wherein the nucleic acid is selected from the group consisting of polynucleotides or fragments thereof shown in (a) to (e) below: (a) (25) A polynucleotide consisting of the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is replaced by t, or a fragment thereof containing 15 or more consecutive bases; (26) A polynucleotide or a fragment thereof containing a deletion, substitution, addition, or insertion of 1 or 2 bases in the polynucleotide or fragment of (25); (27) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (25). (28) A polynucleotide or a fragment thereof according to any one of (25) to (27), comprising a modified nucleic acid and / or a modified nucleotide. (b) a polynucleotide comprising the base sequence represented by SEQ ID NO: 81, or a fragment thereof comprising 15 or more consecutive bases; (c) (29) A polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (30) A polynucleotide or a fragment thereof according to (29), which contains a deletion, substitution, addition, or insertion of 1 or 2 bases. (31) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (29). (32) A polynucleotide or a fragment thereof according to any one of (29) to (31), which comprises a modified nucleic acid and / or a modified nucleotide. (d) a polynucleotide containing a base sequence complementary to the base sequence represented by SEQ ID NO: 81 or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; and (e) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d) or fragments thereof.
7. The device is another liver cancer marker, miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p, miR-6717-5p, miR-6870-5p, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-4286, miR-6877-5p, miR-1225-3p, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p,The group consisting of miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p, miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508, miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6724-5p, miR-6757-5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-44miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16 -5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p, miR-663a, miR- 4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6 087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, m iR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR- The device according to claim 5 or 6, further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
8. The device according to claim 7, wherein the nucleic acid is selected from the group consisting of polynucleotides or fragments thereof shown in (f) to (j) below: (f) (33) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or a base sequence in which u is t in the base sequence, or a fragment thereof containing 15 or more consecutive bases; (34) A polynucleotide or a fragment thereof according to (33), which contains a deletion, substitution, addition, or insertion of 1 or 2 bases. (35) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (33). (36) A polynucleotide or a fragment thereof according to any one of (33) to (35), comprising a modified nucleic acid and / or a modified nucleotide. (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or a fragment thereof comprising 15 or more consecutive bases; (h) (37) A polynucleotide consisting of a base sequence complementary to any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (38) A polynucleotide or a fragment thereof comprising the polynucleotide or the fragment according to (37) above, which contains a deletion, substitution, addition, or insertion of 1 or 2 bases. (39) A polynucleotide or a fragment thereof showing 90% or more identity with the base sequence of the polynucleotide or the fragment of (37). (40) A polynucleotide or a fragment thereof according to any one of (37) to (39), which comprises a modified nucleic acid and / or a modified nucleotide. (i) a polynucleotide containing a base sequence complementary to any of the base sequences represented by SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224, or the base sequence in which u is t, or a fragment thereof containing 15 or more consecutive bases; (j) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i) or fragments thereof.
9. The device according to any one of claims 5 to 8, which is a device for measurement by hybridization technology.
10. The device of claim 9 , wherein the hybridization technology is a nucleic acid array technology.
11. A method for assessing the presence or absence of liver cancer, comprising measuring the expression level of a target nucleic acid in a specimen from a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10, and assessing in vitro whether the subject is affected with liver cancer or not using the measured expression level and a control expression level similarly measured in a healthy subject.
12. The method of claim 11 , wherein the subject is a human.
13. The method of claim 11 or 12, wherein the sample is blood, serum, or plasma.
14. Use of miR-6088 polynucleotide as a liver cancer marker for assessing the presence or absence of liver cancer.
15. The polynucleotide of the aforementioned miR-6088 is miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p, miR-6717-5p, miR-6870-5p, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-31�7, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-4286, miR-6877-5p, miR-1225-3p, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p,The group consisting of miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p, miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508, miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6724-5p, miR-6757-5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR-4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and miR-6836-3p; and / or miR-23b-3p,miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16-5 p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p, miR-663a, miR-4688 , miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6087, mi R-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665 , miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3 p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1 The use according to claim 14, wherein the polynucleotide is used as a liver cancer marker for assessing the presence or absence of liver cancer in combination with at least one polynucleotide selected from the group consisting of miR-238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
16. The at least one polynucleotide is selected from the group consisting of (f) and (g) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224; (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 2 to 21, 23 to 53, 55 to 76, 78 to 80, 82 to 167, 714 to 729, and 168 to 224; 16. The use according to claim 15, wherein the polynucleotide is at least one selected from the group consisting of the polynucleotides
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