Detection kit or device for liver cancer and detection method
By using multiple gene markers specifically bound in the blood in liver cancer detection, a kit and method can significantly detect liver cancer has been developed, which solves the problem of low marker specificity, high invasiveness and high cost in the prior art. and the problem of insufficient sensitivity and specificity, early, high sensitivity and high specificity detection of liver cancer is achieved.
Patent Information
- Application Number
- CN201580032544.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2014-06-18
- Filing Date
- 2015-06-18
- Publication Date
- 2025-02-11
- Estimated Expiration
- 2035-06-18
AI Technical Summary
The prior art has problems in the detection of liver cancer with low marker specificity, high invasiveness of detection methods, and insufficient sensitivity and specificity, making it difficult to detect liver cancer early and improve survival rate.
By finding multiple genes as markers of liver cancer detection from blood that can be collected with low invasiveness, kits and methods that can significantly detect liver cancer using nucleic acids that specifically bind to these markers.
Early, high sensitivity and high specificity detection of liver cancer is achieved, reducing detection costs and invasiveness, and improving the accuracy and survival rate of detection.
Smart Images

Figure CN106459867B_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to a liver cancer detection kit or device for examining whether a subject has liver cancer, comprising a nucleic acid capable of specifically binding to a specific miRNA, and a liver cancer detection method comprising using the nucleic acid to measure the expression level of the miRNA. Background Art
[0002] The liver is the largest organ in the body, located in the right upper abdomen. Its primary functions are to metabolize nutrients and detoxify and excrete harmful substances. According to statistics on cancers of various parts of the body in Japan for 2011, published by the Cancer Countermeasures Information Center of the National Cancer Center, a national research and development corporation, 47,271 people developed liver cancer, meaning that one in 35 Japanese people develops liver cancer, making it the sixth most common cancer site. Furthermore, men are nearly twice as likely to develop liver cancer as women. The combined number of deaths from liver cancer has risen to 30,690, making it the fourth most common cancer site. Furthermore, in the United States, the estimated number of people with liver cancer in 2014 also rose to 33,190, with approximately 23,000 deaths (Non-Patent Document 1).
[0003] Generally speaking, primary liver cancer often refers to hepatocellular carcinoma, which accounts for about 80% of all primary liver cancers. In addition, there are rarer types of cancer such as intrahepatic bile duct carcinoma and bile duct cystic adenocarcinoma, which account for 10% to 20% of all primary liver cancers.
[0004] The progression of liver cancer is defined in Non-Patent Document 2, which categorizes liver cancer into hepatocellular carcinoma and intrahepatic bile duct carcinoma. Specifically, hepatocellular carcinoma is classified into Stage I (T1 / N0 / M0), Stage II (T2 / N0 / M0), Stage IIIA (T3a / N0 / M0), Stage IIIB (T3b / N0 / M0), Stage IIIC (T4 / N0 / M0), Stage IVA (N1 / M0), and Stage IVB (M1), based on the extent of tumor spread (T0-4), lymph node metastasis (N0, N1), and distant metastasis (M0, M1).
[0005] The five-year relative survival rate for liver cancer varies depending on the stage of progression. Non-Patent Document 1 reports a 28% rate for cancer confined to the liver (stages 1, 2, and some stage 3), a 7% rate for cancer with confirmed metastasis near the liver (stages IIIC and IVA), and a 2% rate for cancer with confirmed distant metastasis (stage IVB). Therefore, early detection and treatment of liver cancer, before metastasis is confirmed, would significantly improve survival rates.
[0006] Treatment for liver cancer centers on three main approaches: surgical resection and liver transplantation; localized therapy using puncture to inject drugs or cauterize the cancer; and hepatic artery embolization. Drug therapy and radiation therapy are often used in combination. Particularly in the early stages of liver cancer, when no cancer is found in the blood vessels or surrounding areas, partial liver resection is often used to cure the disease (Non-Patent Document 1). On the other hand, even if the cancer is localized, if it cannot be removed due to reasons such as the large tumor diameter or proximity to blood vessels, liver transplantation is desired. If metastasis is further confirmed, systemic drug therapy and radiation therapy are performed (Non-Patent Document 1).
[0007] As described in Non-Patent Document 1, primary examinations for liver cancer include, in addition to visual inspection and palpation, ultrasound examinations, CT scans, MRI examinations, and imaging examinations such as angiography. Tumor markers used for liver cancer detection include AFP (alpha-fetoprotein) and PIVKA-II (pivka-II), which are often used in conjunction with ultrasound examinations. If liver cancer is suspected based on these primary examinations, a secondary examination involves a pathological examination in which a needle is inserted into the lesion to collect cells and tissues for microscopic examination.
[0008] On the other hand, it is known that the most important cause of liver cancer is long-term infection with hepatitis B and C viruses. Therefore, when liver cancer is suspected, in addition to the above-mentioned tests, hepatitis virus tests may also be performed.
[0009] Although still at the research stage, as shown in Patent Documents 1 to 5, there are reports of methods for detecting liver cancer using the expression levels of microRNA (miRNA) in biological samples such as blood and liver tissue.
[0010] Patent Document 1 discloses a method for detecting leukemia, breast cancer, and liver cancer using hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-92a-2-5p, and hsa-miR-92b-5p, which are miRNAs in tissues, as markers.
[0011] Patent document 2 reports the following method: a method for diagnosing various cancers using miRNAs such as hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, and hsa-miR-486-3p contained in vesicles circulating in body fluids as markers.
[0012] Patent Document 3 discloses a method for detecting various diseases including liver cancer using miRNAs such as hsa-miR-23b-3p, hsa-miR-30c-1-3p, hsa-miR-125a-3p, and hsa-miR-486-3p in tissues and body fluids as markers.
[0013] Patent document 4 shows the following method: a method for detecting various pathological conditions including liver cancer using miRNAs and proteins such as hsa-miR-16-5p, hsa-miR-92a-3p, hsa-miR-663a, hsa-miR-1913, and hsa-miR-625-3p contained in vesicles circulating in body fluids as markers.
[0014] Patent Document 5 shows that hsa-miR-187-5p, hsa-miR-92a-3p, hsa-miR-16-5p, and hsa-miR-30c-1-3p in plasma are markers for colorectal cancer, liver cancer, and lung cancer.
[0015] Prior art literature
[0016] Patent Literature
[0017] Patent Document 1: International Publication No. 2010 / 123043
[0018] Patent Document 2: U.S. Patent Application Publication No. 2011 / 003704
[0019] Patent Document 3: International Publication No. 2010 / 054386
[0020] Patent Document 4: International Publication No. 2012 / 174282
[0021] Patent Document 5: International Publication No. 2011 / 076142
[0022] Non-patent literature
[0023] Non-patent document 1: American Cancer Society “Liver Cancer”, 2013, pp. 5-8, 14-15, 17-23, 27-41
[0024] Non-patent document 2: Sobin, L. et al., "TNM Classification of Malignant Tumours 7th Edition" 2010, p. 104-107
[0025] Non-patent literature 3: HCCN Guidelines "Hepatobiliary Cancer 2nd Edition", 2014, MS-4
[0026] Non-patent document 4: Zhang, B and Yang, B., 1999, Journal of Medical Screening, Vol. 6(2), pp. 108-110
[0027] Non-patent document 5: Takahashi, A. et al., 2008, World Journal of Gastroenterology, Vol. 14(1), pp. 129-31 Summary of the Invention
[0028] Problems to be solved by the invention
[0029] The present invention aims to find a new liver cancer tumor marker and provide a method for efficiently detecting liver cancer using a nucleic acid that can specifically bind to the marker.
[0030] Because liver cancer progresses in a state without liver cancer symptoms, it is a cancer that is difficult to detect in the early stage. In addition, most of the liver is in the right rib, so it is difficult to detect by palpation. Now, for the general public without liver cancer risks such as hepatitis virus infection and cirrhosis, an effective liver cancer screening method has not been established (non-patent literature 1). Ultrasound examination has little burden on the patient and is simple, so it is a widely used liver cancer inspection method, but sometimes detection is difficult depending on the site of occurrence of the cancer. In addition, the test result depends greatly on the skill of the inspection technician, so it is expected to be used together with tumor markers (non-patent literature 3). As a tumor marker for liver cancer detection, AFP is known, but when AFP rises, liver cancer has progressed and cannot be removed or metastasized to the liver. There are many situations (non-patent literature 1). In addition, it has been reported that some liver cancers do not produce AFP. On the other hand, it is known that AFP is a cancer other than liver cancer, such as testicular cancer and ovarian cancer, and further for diseases of the liver that are not cancer, such as persistent hepatitis virus infection, it also rises, so it is considered to be a marker with low specificity (non-patent literature 1). For example, if other cancers are mistakenly diagnosed as liver cancer, the appropriate treatment opportunity may be missed, or the incorrect medical treatment may impose unnecessary financial and physical burdens on the patient. Furthermore, according to the results of a large-scale screening study of hepatitis B infected individuals and those with persistent hepatitis (Non-Patent Document 4), the sensitivity of liver cancer detection using AFP testing was only 69%, making it insufficient for use as a screening test for liver cancer. Furthermore, while CT and MRI tests can effectively detect liver cancer, they require specialized equipment and are expensive, making them unsuitable for widespread use as a single-use test.
[0031] Furthermore, although still in the research stage, there are reports such as the following that liver cancer can be discriminated using the expression levels of microRNA (miRNA) in biological samples such as blood, but none of these reports have been put into practical use.
[0032] Patent Document 1 describes a method for detecting leukemia, breast cancer, and liver cancer using hsa-miR-92a-3p, hsa-miR-92b-3p, hsa-miR-92a-2-5p, and hsa-miR-92b-5p, miRNAs found in blood cells and tissues, as markers. However, this method requires surgical tissue resection to obtain specimens, a procedure that places a heavy physical burden on the patient and is therefore not a suitable diagnostic method. Furthermore, Patent Document 1 does not describe the method's specific performance characteristics, such as accuracy, sensitivity, and specificity, for liver cancer diagnosis, lacking industrial applicability.
[0033] Patent Document 2 reports a method for diagnosing various cancers using miRNAs such as hsa-miR-23a-3p, hsa-miR-23b-3p, hsa-miR-24-3p, hsa-miR-557, hsa-miR-564, hsa-miR-614, hsa-miR-150-3p, and hsa-miR-486-3p, contained in vesicles circulating in body fluids, as markers. However, Patent Document 2 does not describe a specific liver cancer diagnosis method using this detection method, nor does it describe the detection performance, such as accuracy, sensitivity, and specificity, for liver cancer diagnosis. Consequently, this method lacks industrial practicality.
[0034] Patent Document 3 describes a method for detecting various diseases, including liver cancer, using miRNAs such as hsa-miR-23b-3p, hsa-miR-30c-1-3p, hsa-miR-125a-3p, and hsa-miR-486-3p in tissues and body fluids as markers. However, this detection method is based on experimental results in a mouse model and is unclear for detecting liver cancer in humans. Furthermore, Patent Document 3 does not describe the detection performance, such as accuracy, sensitivity, and specificity, for liver cancer diagnosis, thus lacking industrial applicability.
[0035] Patent Document 4 discloses a method for detecting various pathologies, including liver cancer, using miRNAs and proteins such as hsa-miR-16-5p, hsa-miR-92a-3p, hsa-miR-663a, hsa-miR-1913, and hsa-miR-625-3p, contained in vesicles circulating in body fluids, as markers. However, Patent Document 4 does not describe a specific liver cancer diagnostic method using this detection method. Furthermore, these miRNA markers have not been validated using an independent panel of specimens, thus lacking reliability.
[0036] Patent Document 5 lists hsa-miR-187-5p, hsa-miR-92a-3p, hsa-miR-16-5p, and hsa-miR-30c-1-3p in plasma as markers for colorectal cancer, liver cancer, and lung cancer. However, these markers distinguish between a colorectal cancer group and a group consisting of liver cancer, lung cancer, and healthy individuals; they are not markers for detecting liver cancer.
[0037] As such, existing tumor markers have low performance in detecting liver cancer. Furthermore, the performance and detection methods for research-stage markers are not specifically documented. Therefore, their use can lead to unnecessary additional testing due to misidentification of healthy individuals as liver cancer patients, or to missed liver cancer patients, resulting in lost treatment opportunities. Furthermore, measuring dozens to hundreds of miRNAs increases testing costs, making it difficult to use for large-scale screening, such as health checks. Furthermore, collecting liver tissue for tumor marker measurement is highly invasive and undesirable. Therefore, there is a need for liver cancer markers that can be detected using minimally invasive blood samples and accurately distinguish liver cancer patients from healthy subjects. In particular, early detection and treatment of liver cancer can improve survival rates, and partial liver resection is often used to cure liver cancer. Therefore, there is a strong demand for highly sensitive liver cancer markers that can detect even low-grade liver cancer.
[0038] Methods for solving problems
[0039] The present inventors conducted intensive research to solve the above-mentioned problems and found that by identifying multiple genes that can be used as detection markers for liver cancer from blood that can be collected minimally invasively and using nucleic acids that can specifically bind to these genes, liver cancer can be significantly detected, thereby completing the present invention.
[0040] <Overview of the Invention>
[0041] That is, the present invention has the following features.
[0042] (1) 3p、miR-4651、miR-4257、miR-3188、miR-6131、miR-6766-3p、miR-7641、mi R-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-6870-5 p、miR-663b、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-6784-5 p、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, mi R-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5pmiR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p, 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-6798-5pA nucleic acid that specifically binds to at least one polynucleotide selected from miR-3648, miR-4783-3p, and miR-6836-3p.
[0043] (2) The kit according to (1), wherein miR-1343-3p is hsa-miR-1343-3p, miR-6726-5p is hsa-miR-6726-5p, miR-6515-3p is hsa-miR-6515-3p, miR-4651 is hsa-miR-4651, miR-4257 is hsa-miR-4257, miR-3188 is hsa-miR-3188, miR-6131 is hsa-miR-6131, miR-6766-3p is hsa-miR-6766-3p, miR-7641 is hsa-miR-7641, and miR-12 49 is hsa-miR-1249, miR-3679-3p is hsa-miR-3679-3p, miR-6787-5p is hsa-miR-6787-5p, miR-4454 is hsa-miR-4454, miR-3135b is hsa-miR-3135b, miR-6765-3p is hsa-miR-6765-3p, miR-7975 is hsa-miR-7975, miR-204-3p is hsa-miR-204-3p, miR-7977 is hsa-miR-7977, miR-7110-5p is hsa-miR-7110-5p, miR- R-6717-5p is hsa-miR-6717-5p, miR-6870-5p is hsa-miR-6870-5p, miR-663b is hsa-miR-663b, miR-6875-5p is hsa-miR-6875-5p, miR-8072 is hsa-miR-8072, miR-6816-5p is hsa-miR-6816-5p, miR-4281 is hsa-miR-4281, miR-6729-5p is hsa-miR-6729-5p, miR-8069 is hsa-miR-8069, and miR-4706 is hsa-miR-4707. 6, miR-7108-5p was hsa-miR-7108-5p, miR-4433b-3p was hsa-miR-4433b-3p, miR-6893-5p was hsa-miR-6893-5p, miR-6857-5p was hsa-miR-6857-5p, miR-1227-5p was hsa-miR-1227-5p, miR-6741-5p was hsa-miR-6741-5p, miR-451a was hsa-miR-451a, miR-8063 was hsa-miR-8063, miR-3622a-5p was hsa-miR-3622a-5p,miR-615-5p is hsa-miR-615-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-6825-5p is hsa-miR-6825-5p, miR-1260b is hsa-miR-1260b, miR-4433-3p is hsa-miR-4433-3p, miR-4665-5p is hsa-miR-4665-5p, miR-7845-5p is hsa-miR-7845-5p, miR-1908-5p is hsa-miR-1908-5p, miR-6840-3p is hsa-miR-6840-3p, m iR-6765-5p is hsa-miR-6765-5p, miR-296-5p is hsa-miR-296-5p, miR-3675-3p is hsa-miR-3675-3p, miR-6781-5p is hsa-miR-6781-5p, miR-423-5p is hsa-miR-423-5p, miR-3663-3p is hsa-miR-3663-3p, miR-6784-5p is hsa-miR-6784-5p, miR-6749-5p is hsa-miR-6749-5p, miR-1231 is hsa-miR-1231, and miR-4746-5p is hsa-miR-4746-5p. -3p is hsa-miR-4746-3p, miR-6780b-5p is hsa-miR-6780b-5p, miR-4758-5p is hsa-miR-4758-5p, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-6125 is hsa-miR-6125, miR-6721-5p is hsa-miR-6721-5p, miR-6791-5p is hsa-miR-6791-5p, miR-3185 is hsa-miR-3185, and miR-1260a is hsa-miR-1260b. iR-1260a, miR-3197 is hsa-miR-3197, miR-6845-5p is hsa-miR-6845-5p, miR-6887-5p is hsa-miR-6887-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4497 is hsa-miR-4497, miR-1229-5p is hsa-miR-1229-5p, miR-6820-5p is hsa-miR-6820-5p, miR-6777-5p is hsa-miR-6777-5p,miR-3917 is hsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4286 is hsa-miR-4286, miR-6877-5p is hsa-miR-6877-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6088 is hsa-miR-6088, miR-6800-5p is hsa-miR-6800-5p, miR-1246 is hsa-miR-1246, miR-4467 is hsa-miR-4467, miR-4419b is hsa-miR-4419b, and miR-1914- 3p is hsa-miR-1914-3p, miR-4632-5p is hsa-miR-4632-5p, miR-1915-5p is hsa-miR-1915-5p, miR-3940-5p is hsa-miR-3940-5p, miR-1185-2-3p is hsa-miR-1185-2-3p, miR-6746-5p is hsa-miR-6746-5p, miR-5001-5p is hsa-miR-5001-5p, miR-1228-5p is hsa-miR-1228-5p, miR-5572 is hsa-miR-5572, and miR-4327-5p is hsa-miR-5327-5p. is hsa-miR-4327, miR-4638-5p is hsa-miR-4638-5p, miR-6799-5p is hsa-miR-6799-5p, miR-6861-5p is hsa-miR-6861-5p, miR-6727-5p is hsa-miR-6727-5p, miR-4513 is hsa-miR-4513, miR-6805-3p is hsa-miR-6805-3p, miR-6808-5p is hsa-miR-6808-5p, miR-4449 is hsa-miR-4449, and miR-1199-5p is hsa-miR-119 9-5p, miR-1275 is hsa-miR-1275, miR-4792 is hsa-miR-4792, miR-4443 is hsa-miR-4443, miR-6891-5p is hsa-miR-6891-5p, miR-6826-5p is hsa-miR-6826-5p, miR-6807-5p is hsa-miR-6807-5p, miR-7150 is hsa-miR-7150, miR-4534 is hsa-miR-4534, miR-4476 is hsa-miR-4476, miR-4649-5p is hsa-miR4649-5p,miR-4525 is hsa-miR-4525, miR-1915-3p is hsa-miR-1915-3p, miR-4516 is hsa-miR-4516, miR-4417 is hsa-miR-4417, miR-642b-3p is hsa-miR-642b-3p, miR-3141 is hsa-miR-3141, miR-5100 is hsa-miR-5100, miR-6848-5p is hsa-miR-6848-5p, miR-4739 is hsa-miR-4739, miR-4459 is hsa-miR-4459, and miR-123 is hsa-miR-123. 7-5p is hsa-miR-1237-5p, miR-296-3p is hsa-miR-296-3p, miR-4665-3p is hsa-miR-4665-3p, miR-6786-5p is hsa-miR-6786-5p, miR-4258 is hsa-miR-4258, miR-6510-5p is hsa-miR-6510-5p, miR-1343-5p is hsa-miR-1343-5p, miR-1247-3p is hsa-miR-1247-3p, miR-6805-5p is hsa-miR-6805-5p, miR-4492-5p is hsa-miR-4492-5p. for hsa-miR-4492, miR-1469 for hsa-miR-1469, miR-1268b for hsa-miR-1268b, miR-6858-5p for hsa-miR-6858-5p, miR-3937 for hsa-miR-3937, miR-939-5p for hsa-miR-939-5p, miR-3656 for hsa-miR-3656, miR-744-5p for hsa-miR-744-5p, miR-4687-3p for hsa-miR-4687-3p, miR-4763-3p for hsa-miR-4763-3p, and miR-3 620-5p is hsa-miR-3620-5p, miR-3195 is hsa-miR-3195, miR-6842-5p is hsa-miR-6842-5p, miR-4707-5p is hsa-miR-4707-5p, miR-642a-3p is hsa-miR-642a-3p, miR-7113-3p is hsa-miR-7113-3p, miR-4728-5p is hsa-miR-4728-5p, miR-5195-3p is hsa-miR-5195-3p, miR-1185-1-3p is hsa-miR-1185-1-3p,miR-6774-5p is hsa-miR-6774-5p, miR-8059 is hsa-miR-8059, miR-3131 is hsa-miR-3131, miR-7847-3p is hsa-miR-7847-3p, miR-4463 is hsa-miR-4463, 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, miR-7111-5p is hsa-miR-7111-5p, miR-6782-5p is hsa-miR-6782-5p, miR-4734 is hsa-miR-4734, miR-3162-5p is hsa-miR-3162-5p, miR-887-3p is hsa-miR-887-3p, miR-6752-5p is hsa-miR-6752-5p, miR-6724-5p is hsa-miR-6724-5p, miR-67 57-5p is hsa-miR-6757-5p, miR-4448 is hsa-miR-4448, miR-671-5p is hsa-miR-671-5p, miR-3178 is hsa-miR-3178, miR-4725-3p is hsa-miR-4725-3p, miR-940 is hsa-miR-940, miR-6789-5p is hsa-miR-6789-5p, miR-4484 is hsa-miR-4484, miR-4634 is hsa-miR-4634 for hsa-miR-4634, miR-4745-5p for hsa-miR-4745-5p, miR-4730 for hsa-miR-4730, miR-6803-5p for hsa-miR-6803-5p, miR-6798-5p for hsa-miR-6798-5p, miR-3648 for hsa-miR-3648, miR-4783-3p for hsa-miR-4783-3p, and miR-6836-3p for hsa-miR-6836-3p. ,
[0044] (3) The kit according to (1) or (2), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a) to (e),
[0045] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0046] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729,
[0047] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0048] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, and
[0049] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0050] (4) The kit according to any one of (1) to (3), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of miR-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 and miR-663a, which are other liver cancer markers.
[0051] (5) The kit according to (4), wherein miR-23b-3p is hsa-miR-23b-3p, miR-23a-3p is hsa-miR-23a-3p, miR-625-3p is hsa-miR-625-3p, miR-1228-3p is hsa-miR-1228-3p, miR-614 is hsa-miR-614, miR-1913 is hsa-miR-1913, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-187-5p is hsa -miR-187-5p, miR-16-5p is hsa-miR-16-5p, miR-92b-3p is hsa-miR-92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is hsa-miR-564, miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-92a-3p is hsa-miR-92a-3p and miR-663a is hsa-miR-663a.
[0052] (6) The kit according to (4) or (5), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (j),
[0053] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0054] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 168 to 183,
[0055] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0056] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, and
[0057] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0058] (7) The kit according to any one of (1) to (6), further comprising a protein selected from the group consisting of 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, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR- A nucleic acid that specifically binds to at least one of the polynucleotides selected from the group consisting of 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, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
[0059] (8) The kit according to (7), wherein miR-4688 is hsa-miR-4688, miR-4648 is hsa-miR-4648, miR-6085 is hsa-miR-6085, miR-6126 is hsa-miR-6126, miR-6880-5p is hsa-miR-6880-5p, miR-328-5p is hsa-miR-328-5p, miR-6768-5p is hsa-miR-6768-5p, miR-3180 is hsa-miR-3180, miR-6087 is hsa-miR-6087, and miR-1273g-3p is hsa- miR-1273g-3p, miR-1225-5p is hsa-miR-1225-5p, miR-3196 is hsa-miR-3196, miR-4695-5p is hsa-miR-4695-5p, miR-6732-5p is hsa-miR-6732-5p, miR-638 is hsa-miR-638, miR-6813-5p is hsa-miR-6813-5p, miR-665 is hsa-miR-665, miR-486-3p is hsa-miR-486-3p, miR-4466 is hsa-miR-4466, miR-30c-1-3p is hsa-miR-30c-3p hsa-miR-30c-1-3p, miR-3621 is hsa-miR-3621, miR-6743-5p is hsa-miR-6743-5p, miR-4298 is hsa-miR-4298, miR-4741 is hsa-miR-4741, miR-3619-3p is hsa-miR-3619-3p, miR-6824-5p is hsa-miR-6824-5p, miR-5698 is hsa-miR-5698, miR-371a-5p is hsa-miR-371a-5p, miR-4488 is hsa-miR4488, miR-1233- 5p is hsa-miR-1233-5p, miR-4723-5p is hsa-miR-4723-5p, miR-24-3p is hsa-miR-24-3p, miR-1238-5p is hsa-miR-1238-5p, miR-4442 is hsa-miR-4442, miR-3928-3p is hsa-miR-3928-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6089 is hsa-miR-6089, miR-6124 is hsa-miR-6124, miR-6778-5p is hsa-miR-6778-5p,miR-557 is hsa-miR-557 and miR-6090 is hsa-miR-6090.
[0060] (9) The kit according to (7) or (8), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (k) to (o),
[0061] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0062] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 184 to 224,
[0063] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0064] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, and
[0065] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0066] (10) The kit according to any one of (1) to (9), comprising at least two nucleic acids capable of specifically binding to at least two polynucleotides selected from all the liver cancer markers described in (1) or (2).
[0067] (11) Device for detecting liver cancer, comprising a substance capable of binding to a selected from miR-1343-3p, 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-663b, 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-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-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-44miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p, 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-6798-5pA nucleic acid that specifically binds to at least one polynucleotide selected from miR-3648, miR-4783-3p, and miR-6836-3p.
[0068] (12) The device according to (11), wherein miR-1343-3p is hsa-miR-1343-3p, miR-6726-5p is hsa-miR-6726-5p, miR-6515-3p is hsa-miR-6515-3p, miR-4651 is hsa-miR-4651, miR-4257 is hsa-miR-4257, miR-3188 is hsa-miR-3188, miR-6131 is hsa-miR-6131, miR-6766-3p is hsa-miR-6766-3p, miR-7641 is hsa-miR-7641, and miR-12 49 is hsa-miR-1249, miR-3679-3p is hsa-miR-3679-3p, miR-6787-5p is hsa-miR-6787-5p, miR-4454 is hsa-miR-4454, miR-3135b is hsa-miR-3135b, miR-6765-3p is hsa-miR-6765-3p, miR-7975 is hsa-miR-7975, miR-204-3p is hsa-miR-204-3p, miR-7977 is hsa-miR-7977, miR-7110-5p is hsa-miR-7110-5p, miR- R-6717-5p is hsa-miR-6717-5p, miR-6870-5p is hsa-miR-6870-5p, miR-663b is hsa-miR-663b, miR-6875-5p is hsa-miR-6875-5p, miR-8072 is hsa-miR-8072, miR-6816-5p is hsa-miR-6816-5p, miR-4281 is hsa-miR-4281, miR-6729-5p is hsa-miR-6729-5p, miR-8069 is hsa-miR-8069, and miR-4706 is hsa-miR-4707. 6, miR-7108-5p was hsa-miR-7108-5p, miR-4433b-3p was hsa-miR-4433b-3p, miR-6893-5p was hsa-miR-6893-5p, miR-6857-5p was hsa-miR-6857-5p, miR-1227-5p was hsa-miR-1227-5p, miR-6741-5p was hsa-miR-6741-5p, miR-451a was hsa-miR-451a, miR-8063 was hsa-miR-8063, miR-3622a-5p was hsa-miR-3622a-5p,miR-615-5p is hsa-miR-615-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-6825-5p is hsa-miR-6825-5p, miR-1260b is hsa-miR-1260b, miR-4433-3p is hsa-miR-4433-3p, miR-4665-5p is hsa-miR-4665-5p, miR-7845-5p is hsa-miR-7845-5p, miR-1908-5p is hsa-miR-1908-5p, miR-6840-3p is hsa-miR-6840-3p, m iR-6765-5p is hsa-miR-6765-5p, miR-296-5p is hsa-miR-296-5p, miR-3675-3p is hsa-miR-3675-3p, miR-6781-5p is hsa-miR-6781-5p, miR-423-5p is hsa-miR-423-5p, miR-3663-3p is hsa-miR-3663-3p, miR-6784-5p is hsa-miR-6784-5p, miR-6749-5p is hsa-miR-6749-5p, miR-1231 is hsa-miR-1231, and miR-4746-5p is hsa-miR-4746-5p. -3p is hsa-miR-4746-3p, miR-6780b-5p is hsa-miR-6780b-5p, miR-4758-5p is hsa-miR-4758-5p, miR-3679-5p is hsa-miR-3679-5p, miR-3184-5p is hsa-miR-3184-5p, miR-6125 is hsa-miR-6125, miR-6721-5p is hsa-miR-6721-5p, miR-6791-5p is hsa-miR-6791-5p, miR-3185 is hsa-miR-3185, and miR-1260a is hsa-miR-1260b. iR-1260a, miR-3197 is hsa-miR-3197, miR-6845-5p is hsa-miR-6845-5p, miR-6887-5p is hsa-miR-6887-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6872-3p is hsa-miR-6872-3p, miR-4497 is hsa-miR-4497, miR-1229-5p is hsa-miR-1229-5p, miR-6820-5p is hsa-miR-6820-5p, miR-6777-5p is hsa-miR-6777-5p,miR-3917 is hsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4286 is hsa-miR-4286, miR-6877-5p is hsa-miR-6877-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6088 is hsa-miR-6088, miR-6800-5p is hsa-miR-6800-5p, miR-1246 is hsa-miR-1246, miR-4467 is hsa-miR-4467, miR-4419b is hsa-miR-4419b, and miR-1914- 3p is hsa-miR-1914-3p, miR-4632-5p is hsa-miR-4632-5p, miR-1915-5p is hsa-miR-1915-5p, miR-3940-5p is hsa-miR-3940-5p, miR-1185-2-3p is hsa-miR-1185-2-3p, miR-6746-5p is hsa-miR-6746-5p, miR-5001-5p is hsa-miR-5001-5p, miR-1228-5p is hsa-miR-1228-5p, miR-5572 is hsa-miR-5572, and miR-4327-5p is hsa-miR-5327-5p. is hsa-miR-4327, miR-4638-5p is hsa-miR-4638-5p, miR-6799-5p is hsa-miR-6799-5p, miR-6861-5p is hsa-miR-6861-5p, miR-6727-5p is hsa-miR-6727-5p, miR-4513 is hsa-miR-4513, miR-6805-3p is hsa-miR-6805-3p, miR-6808-5p is hsa-miR-6808-5p, miR-4449 is hsa-miR-4449, and miR-1199-5p is hsa-miR-119 9-5p, miR-1275 is hsa-miR-1275, miR-4792 is hsa-miR-4792, miR-4443 is hsa-miR-4443, miR-6891-5p is hsa-miR-6891-5p, miR-6826-5p is hsa-miR-6826-5p, miR-6807-5p is hsa-miR-6807-5p, miR-7150 is hsa-miR-7150, miR-4534 is hsa-miR-4534, miR-4476 is hsa-miR-4476, miR-4649-5p is hsa-miR4649-5p,miR-4525 is hsa-miR-4525, miR-1915-3p is hsa-miR-1915-3p, miR-4516 is hsa-miR-4516, miR-4417 is hsa-miR-4417, miR-642b-3p is hsa-miR-642b-3p, miR-3141 is hsa-miR-3141, miR-5100 is hsa-miR-5100, miR-6848-5p is hsa-miR-6848-5p, miR-4739 is hsa-miR-4739, miR-4459 is hsa-miR-4459, and miR-123 is hsa-miR-123. 7-5p is hsa-miR-1237-5p, miR-296-3p is hsa-miR-296-3p, miR-4665-3p is hsa-miR-4665-3p, miR-6786-5p is hsa-miR-6786-5p, miR-4258 is hsa-miR-4258, miR-6510-5p is hsa-miR-6510-5p, miR-1343-5p is hsa-miR-1343-5p, miR-1247-3p is hsa-miR-1247-3p, miR-6805-5p is hsa-miR-6805-5p, miR-4492-5p is hsa-miR-4492-5p. for hsa-miR-4492, miR-1469 for hsa-miR-1469, miR-1268b for hsa-miR-1268b, miR-6858-5p for hsa-miR-6858-5p, miR-3937 for hsa-miR-3937, miR-939-5p for hsa-miR-939-5p, miR-3656 for hsa-miR-3656, miR-744-5p for hsa-miR-744-5p, miR-4687-3p for hsa-miR-4687-3p, miR-4763-3p for hsa-miR-4763-3p, and miR-3 620-5p is hsa-miR-3620-5p, miR-3195 is hsa-miR-3195, miR-6842-5p is hsa-miR-6842-5p, miR-4707-5p is hsa-miR-4707-5p, miR-642a-3p is hsa-miR-642a-3p, miR-7113-3p is hsa-miR-7113-3p, miR-4728-5p is hsa-miR-4728-5p, miR-5195-3p is hsa-miR-5195-3p, miR-1185-1-3p is hsa-miR-1185-1-3p,miR-6774-5p is hsa-miR-6774-5p, miR-8059 is hsa-miR-8059, miR-3131 is hsa-miR-3131, miR-7847-3p is hsa-miR-7847-3p, miR-4463 is hsa-miR-4463, 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, miR-7111-5p is hsa-miR-7111-5p, miR-6782-5p is hsa-miR-6782-5p, miR-4734 is hsa-miR-4734, miR-3162-5p is hsa-miR-3162-5p, miR-887-3p is hsa-miR-887-3p, miR-6752-5p is hsa-miR-6752-5p, miR-6724-5p is hsa-miR-6724-5p, miR-67 57-5p is hsa-miR-6757-5p, miR-4448 is hsa-miR-4448, miR-671-5p is hsa-miR-671-5p, miR-3178 is hsa-miR-3178, miR-4725-3p is hsa-miR-4725-3p, miR-940 is hsa-miR-940, miR-6789-5p is hsa-miR-6789-5p, miR-4484 is hsa-miR-4484, miR-4634 is hsa-miR-4634 for hsa-miR-4634, miR-4745-5p for hsa-miR-4745-5p, miR-4730 for hsa-miR-4730, miR-6803-5p for hsa-miR-6803-5p, miR-6798-5p for hsa-miR-6798-5p, miR-3648 for hsa-miR-3648, miR-4783-3p for hsa-miR-4783-3p, and miR-6836-3p for hsa-miR-6836-3p. ,
[0069] (13) The device according to (11) or (12), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a) to (e),
[0070] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0071] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729,
[0072] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0073] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, and
[0074] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0075] (14) The device according to any one of (11) to (13), further comprising a nucleic acid capable of specifically binding to at least one polynucleotide selected from the group consisting of 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 and miR-663a, which are other liver cancer markers.
[0076] (15) The device according to (14), wherein miR-23b-3p is hsa-miR-23b-3p, miR-23a-3p is hsa-miR-23a-3p, miR-625-3p is hsa-miR-625-3p, miR-1228-3p is hsa-miR-1228-3p, miR-614 is hsa-miR-614, miR-1913 is hsa-miR-1913, miR-92a-2-5p is hsa-miR-92a-2-5p, and miR-187-5p is hsa -miR-187-5p, miR-16-5p is hsa-miR-16-5p, miR-92b-3p is hsa-miR-92b-3p, miR-150-3p is hsa-miR-150-3p, miR-564 is hsa-miR-564, miR-125a-3p is hsa-miR-125a-3p, miR-92b-5p is hsa-miR-92b-5p, miR-92a-3p is hsa-miR-92a-3p and miR-663a is hsa-miR-663a.
[0077] (16) The device according to (14) or (15), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (f) to (j),
[0078] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0079] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 168 to 183,
[0080] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0081] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, and
[0082] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0083] (17) The device according to any one of (11) to (16), further comprising a protein capable of interacting with other liver cancer markers selected from 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, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR- A nucleic acid that specifically binds to at least one of the polynucleotides selected from the group consisting of 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, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
[0084] (18) The device according to (17), wherein miR-4688 is hsa-miR-4688, miR-4648 is hsa-miR-4648, miR-6085 is hsa-miR-6085, miR-6126 is hsa-miR-6126, miR-6880-5p is hsa-miR-6880-5p, miR-328-5p is hsa-miR-328-5p, miR-6768-5p is hsa-miR-6768-5p, miR-3180 is hsa-miR-3180, miR-6087 is hsa-miR-6087, and miR-1273g-3p is hsa -miR-1273g-3p, miR-1225-5p is hsa-miR-1225-5p, miR-3196 is hsa-miR-3196, miR-4695-5p is hsa-miR-4695-5p, miR-6732-5p is hsa-miR-6732-5p, miR-638 is hsa-miR-638, miR-6813-5p is hsa-miR-6813-5p, miR-665 is hsa-miR-665, miR-486-3p is hsa-miR-486-3p, miR-4466 is hsa-miR-4466, miR-30c-1-3p is hsa-miR-30c-3p hsa-miR-30c-1-3p, miR-3621 is hsa-miR-3621, miR-6743-5p is hsa-miR-6743-5p, miR-4298 is hsa-miR-4298, miR-4741 is hsa-miR-4741, miR-3619-3p is hsa-miR-3619-3p, miR-6824-5p is hsa-miR-6824-5p, miR-5698 is hsa-miR-5698, miR-371a-5p is hsa-miR-371a-5p, miR-4488 is hsa-miR4488, miR-1233- 5p is hsa-miR-1233-5p, miR-4723-5p is hsa-miR-4723-5p, miR-24-3p is hsa-miR-24-3p, miR-1238-5p is hsa-miR-1238-5p, miR-4442 is hsa-miR-4442, miR-3928-3p is hsa-miR-3928-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6089 is hsa-miR-6089, miR-6124 is hsa-miR-6124, miR-6778-5p is hsa-miR-6778-5p,miR-557 is hsa-miR-557 and miR-6090 is hsa-miR-6090.
[0085] (19) The device according to (17) or (18), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (k) to (o),
[0086] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0087] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 184 to 224,
[0088] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0089] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, and
[0090] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0091] (20) The device according to any one of (11) to (19), which is a device for performing measurements using hybridization technology.
[0092] (21) The device according to (20), wherein the hybridization technology is nucleic acid array technology.
[0093] (22) The device according to any one of (11) to (21), comprising at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides selected from all liver cancer markers described in (11) or (12).
[0094] (23) A method for detecting liver cancer, comprising: using the kit described in any one of (1) to (10) or the device described in any one of (11) to (22) to measure the expression level of the target nucleic acid in a specimen of a subject, and using the measured expression level and a control expression level measured in a similar manner in a healthy subject to perform in vitro evaluation of whether the subject has liver cancer or not.
[0095] (24) The method according to (23), wherein the subject is a human.
[0096] (25) The method according to (23) or (24), wherein the specimen is blood, serum or plasma.
[0097] <Definition of terms>
[0098] The terms used in this specification have the following definitions.
[0099] The display of abbreviations such as nucleotide, polynucleotide, DNA, RNA, etc. follows the "Guidelines for the Preparation of Specifications, etc. Containing Base Sequences or Amino Acid Sequences" (compiled by the Japan Patent Office) and the common practice in this technical field.
[0100] In this specification, the term "polynucleotide" is used for a nucleic acid containing any one of RNA, DNA, and RNA / DNA (chimera). In addition, the above DNA includes any one of cDNA, genomic DNA, and synthetic DNA. Further, the above RNA includes any one of total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. In this specification, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced based on a specified base sequence (which can be either a natural-type sequence or a non-natural-type sequence), for example, using an automatic nucleic acid synthesizer. The term "non-natural-type sequence" in this specification is intended to be used in a broad sense and includes sequences different from natural-type sequences, such as sequences containing one or more nucleotide substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), etc. In addition, in this specification, polynucleotide and nucleic acid are used interchangeably.
[0101] In this specification, a "fragment" is a polynucleotide having a base sequence that is a continuous part of a polynucleotide, desirably having a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more.
[0102] In this specification, the term "gene" is intended to be used not only for RNA and double-stranded DNA but also for each single-stranded DNA such as the sense strand (or coding strand) or the complementary strand (or antisense strand) constituting them. In addition, its length is not particularly limited.
[0103] Therefore, in this specification, "gene", unless otherwise specified, includes: double-stranded DNA comprising human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand) comprising cDNA having a sequence complementary to the positive strand, microRNA (miRNA), and any of their fragments and transcription products. In addition, the "gene" is not only the "gene" shown by a specific base sequence (or sequence number), but also includes RNA having the same biological function as the RNA encoded by the gene, such as "nucleic acid" encoding homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. As such "nucleic acid" encoding homologs, mutants or derivatives, specifically, there can be mentioned "nucleic acid" having a base sequence that hybridizes with the base sequence shown in any one of SEQ ID NOs. 1 to 765, or the complementary sequence of the base sequence in which u is t in the base sequence under the stringent conditions described below. In addition, "gene" may include, for example, expression control regions, coding regions, exons or introns, regardless of the difference in functional regions. Furthermore, the "gene" may be contained in cells, released outside the cells and exist independently, or may be enclosed in small vesicles called exosomes.
[0104] As used herein, "exosomes" are small vesicles surrounded by a lipid bilayer secreted by cells. Exosomes originate from multivesicular endosomes and, when released into the extracellular environment, may contain biological substances such as "genes" such as RNA and DNA, as well as proteins. Exosomes are known to be present in body fluids such as blood, serum, plasma, serum, and lymph.
[0105] As used herein, "transcript" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a region upstream of the gene called the promoter, synthesizing RNA in a manner complementary to the base sequence of the DNA, with ribonucleotides attached to the 3' end. This RNA contains not only the gene itself but also the entire sequence from the transcription start point to the end of the poly A sequence, represented by expression control regions, coding regions, exons, or introns.
[0106] In addition, as used herein, "microRNA (miRNA)" is intended to be used as a 15-25 base non-coding RNA that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleavage enzyme with RNase III cleavage activity, and incorporated into a protein complex called RISC, thereby participating in the translational repression of mRNA, unless otherwise specified. Furthermore, the "miRNA" used herein includes not only "miRNAs" represented by specific base sequences (or sequence numbers), but also precursors (pre-miRNA, pri-miRNA) of such "miRNAs," as well as miRNAs with equivalent biological functions, such as homologs (i.e., homologs or orthologs), mutants due to genetic polymorphisms, and derivatives. Specifically, examples of such precursors, homologs, mutants, or derivatives include "miRNAs" that can be identified by miRBase version 20 (http: / / www.mirbase.org / ) and that hybridize under stringent conditions described below to the complementary sequence of any of the specific base sequences represented by any of SEQ ID NOs. 1 to 765. In addition, the "miRNA" used in this specification can be a gene product of a miR gene, such a gene product comprising a mature miRNA (for example, a non-coding RNA of 15 to 25 bases or 19 to 25 bases involved in translational inhibition of mRNA as described above) or a miRNA precursor (for example, a pre-miRNA or pri-miRNA as described above).
[0107] The term "probe" herein includes a polynucleotide for specifically detecting RNA produced by gene expression or a polynucleotide derived from the RNA and / or a polynucleotide complementary thereto.
[0108] The term "primer" as used herein includes a polynucleotide that specifically recognizes and amplifies RNA produced by gene expression or a polynucleotide derived from the RNA and / or a polynucleotide complementary thereto.
[0109] Here, a complementary polynucleotide (complementary strand, minus strand) refers to a polynucleotide that is complementary to the full-length sequence of a polynucleotide consisting of a base sequence defined by any of SEQ ID NOs: 1 to 765, or a base sequence in which u is t in such a base sequence, or a partial sequence thereof (herein referred to as the plus strand for convenience), based on base pair relationships such as A:T(U) and G:C. However, such a complementary strand is not limited to being completely complementary to the base sequence of the target plus strand and may also be complementary to the extent that it can hybridize with the target plus strand under stringent conditions.
[0110] As used herein, "stringent conditions" refer to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater degree (e.g., the average of the background values + the standard error of the background values × 2 or greater) than to other sequences. Stringent conditions are sequence-dependent and vary depending on the hybridization environment. By controlling the stringency of hybridization and / or washing conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.
[0111] The "Tm value" herein refers to the temperature at which the double-stranded portion of a polynucleotide denatures into a single strand and the double strands and single strands exist in a 1:1 ratio.
[0112] As used herein, "mutant" refers to a natural mutant caused by polymorphism, mutation, etc. in the case of nucleic acids, or a mutant comprising a deletion, substitution, addition, or insertion of one or more bases in any of the base sequences of SEQ ID NOs. 1 to 765, or a base sequence in which u is t in the base sequence, or a partial sequence thereof, or a mutant showing a % identity of about 90% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more with the respective base sequences or partial sequences thereof, or a nucleic acid that hybridizes with a polynucleotide or oligonucleotide comprising the base sequence or a partial sequence thereof under the stringent conditions defined above.
[0113] In this specification, "a plurality of" refers to an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.
[0114] In this specification, mutants can be prepared using known techniques such as site-directed mutagenesis and mutation introduction using PCR.
[0115] As used herein, "% identity" can be determined using the above-mentioned protein or gene search systems utilizing BLAST or FASTA, with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, pp. 203-214; Altschul, SF et al., 1990, Journal of Molecular Biology, Vol. 215, pp. 403-410; Pearson, WR et al., 1988, Proc. Natl. Acad. Sci. USA, Vol. 85, pp. 2444-2448).
[0116] In this specification, "derivative" refers to modified nucleic acids, and includes, but is not limited to, derivatives labeled with fluorophores, etc., derivatives containing modified nucleotides (for example, nucleotides containing groups such as halogens, alkyl groups such as methyl groups, alkoxy groups such as methoxy groups, thio groups, carboxymethyl groups, and nucleotides that have undergone base reconstruction, double bond saturation, deamination, replacement of oxygen molecules with sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, PE et al., 1991, Science, Vol. 254, p1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p5401-5404), etc.
[0117] In this specification, the "nucleic acid" that can specifically bind to a polynucleotide selected from the group of miRNAs as liver cancer markers is a synthetic or modulated nucleic acid, specifically, a "nucleic acid probe" or "primer" that is used directly or indirectly to detect the presence of liver cancer in a subject, or to diagnose the presence of liver cancer, the extent of the disease, the improvement of liver cancer, the degree of improvement, the sensitivity to liver cancer treatment, or to screen for candidate substances useful for the prevention, improvement or treatment of liver cancer. They include nucleotides, oligonucleotides and polynucleotides that can specifically recognize and bind to the transcripts shown in any one of sequence numbers 1 to 765 or their cDNA synthetic nucleic acids in a living body, especially in a specimen such as blood, urine or other body fluids related to the development of liver cancer. Based on the above properties, these nucleotides, oligonucleotides and polynucleotides can be effectively used as probes for detecting the above genes expressed in vivo, in tissues, cells, etc., and can also be effectively used as primers for amplifying the above genes expressed in vivo.
[0118] The term "detection" used in this specification can be replaced with the term "inspection," "measurement," "detection," or "determination support." Furthermore, the term "evaluation" used in this specification includes supporting diagnosis or evaluation based on the results of an inspection or measurement.
[0119] As used herein, the term "subject" refers to mammals, including humans, primates such as chimpanzees, pets such as dogs and cats, livestock such as cattle, horses, sheep, and goats, and rodents such as mice and rats. Furthermore, the term "healthy subject" refers to a mammal that does not have the cancer being tested.
[0120] The term "liver cancer" as used herein refers to "primary liver cancer" originating in the liver, and includes, for example, "hepatocellular carcinoma" and "mixed hepatocellular-cholangiocarcinoma" in which liver cells have become cancerous.
[0121] As used herein, "P" or "P-value" indicates the probability of observing a statistically significant difference compared to the statistic calculated from the data under the null hypothesis in a statistical test. Therefore, a smaller "P" or "P-value" indicates a significant difference between the comparison subjects.
[0122] In this specification, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, liver cancer can be detected early, leading to complete resection of the cancer site and a reduction in the recurrence rate.
[0123] As used herein, "specificity" refers to (number of true negatives) / (number of true negatives + number of false positives). High specificity prevents unnecessary additional testing due to misidentification of healthy individuals as liver cancer patients, thereby reducing the burden on patients and medical expenses.
[0124] In this specification, "accuracy" refers to the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the proportion of correct discrimination results for all samples and is the primary indicator for evaluating detection performance.
[0125] As used herein, "specimens" as the subject of assessment, detection, or diagnosis refer to tissues and biological materials whose gene expression changes as liver cancer develops, progresses, and as treatment for the disease manifests. Specifically, these refer to liver tissue and its surrounding blood vessels, lymph nodes, and internal organs. Furthermore, these refer to suspected metastatic organs, skin, and body fluids such as blood, urine, saliva, sweat, and tissue extracts; serum and plasma prepared from blood; feces; and hair. Furthermore, these refer to biological samples extracted from these materials, specifically genes such as RNA and miRNA.
[0126] As used herein, the term "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" includes the hsa-miR-1343-3p gene described in SEQ ID NO: 1 (miRBase Accession No. MIMAT0019776) and homologs or orthologs in other species. The hsa-miR-1343-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-1343-3p", "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 225) is known to have a hairpin-like structure.
[0127] As used herein, the term "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" includes the hsa-miR-6726-5p gene described in SEQ ID NO: 2 (miRBase Accession No. MIMAT0027353) and homologs or orthologs in other species. The hsa-miR-6726-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6726-5p", "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 226) is known to have a hairpin-like structure.
[0128] As used herein, the term "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" includes the hsa-miR-6515-3p gene described in SEQ ID NO: 3 (miRBase Accession No. MIMAT0025487) and homologs or orthologs in other species. The hsa-miR-6515-3p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, Vol. 20, pp. 4025-4040. Furthermore, as a precursor of "hsa-miR-6515-3p", "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 227) is known to have a hairpin-like structure.
[0129] As used herein, the term "hsa-miR-4651 gene" or "hsa-miR-4651" includes the hsa-miR-4651 gene described in SEQ ID NO: 4 (miRBase Accession No. MIMAT0019715) and homologs or orthologs in other species. The hsa-miR-4651 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4651," "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 228) is known to have a hairpin-like structure.
[0130] As used herein, the term “hsa-miR-4257 gene” or “hsa-miR-4257” includes the hsa-miR-4257 gene described in SEQ ID NO: 5 (miRBase Accession No. MIMAT0016878) and homologs or orthologs in other species. The hsa-miR-4257 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4257”, “hsa-mir-4257” (miRBase Accession No. MI0015856, SEQ ID NO: 229) is known to have a hairpin-like structure.
[0131] As used herein, the term “hsa-miR-3188 gene” or “hsa-miR-3188” includes the hsa-miR-3188 gene described in SEQ ID NO: 6 (miRBase Accession No. MIMAT0015070) and homologs or orthologs in other species. The hsa-miR-3188 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3188,” “hsa-mir-3188” (miRBase Accession No. MI0014232, SEQ ID NO: 230) is known to have a hairpin-like structure.
[0132] As used herein, the term "hsa-miR-6131 gene" or "hsa-miR-6131" includes the hsa-miR-6131 gene described in SEQ ID NO: 7 (miRBase Accession No. MIMAT0024615) and homologs or orthologs in other species. The hsa-miR-6131 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, 4, pp. 552-564. Furthermore, as a precursor of "hsa-miR-6131," "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 231) is known to have a hairpin-like structure.
[0133] As used herein, the term "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" includes the hsa-miR-6766-3p gene described in SEQ ID NO: 8 (miRBase Accession No. MIMAT0027433) and homologs or orthologs in other species. The hsa-miR-6766-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6766-3p", "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 232) is known to have a hairpin-like structure.
[0134] As used herein, the term “hsa-miR-7641 gene” or “hsa-miR-7641” includes the hsa-miR-7641 gene described in SEQ ID NO: 9 (miRBase Accession No. MIMAT0029782) and homologs or orthologs of other biological species. The hsa-miR-7641 gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, Vol. 36, pp. 353-358. In addition, as precursors of “hsa-miR-7641”, “hsa-mir-7641-1” and “hsa-mir-7641-2” (miRBase Accession Nos. MI0024975, MI0024976, SEQ ID NOs: 233, 234) are known as hairpin-like structure precursors.
[0135] As used herein, the term “hsa-miR-1249 gene” or “hsa-miR-1249” includes the hsa-miR-1249 gene described in SEQ ID NO: 10 (miRBase Accession No. MIMAT0005901) and homologs or orthologs in other biological species. The hsa-miR-1249 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1249”, “hsa-mir-1249” (miRBase Accession No. MI0006384, SEQ ID NO: 235) is known to have a hairpin-like structure.
[0136] As used herein, the term "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" includes the hsa-miR-3679-3p gene described in SEQ ID NO: 11 (miRBase Accession No. MIMAT0018105) and homologs or orthologs in other species. The hsa-miR-3679-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of "hsa-miR-3679-3p", "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 236) is known to have a hairpin-like structure.
[0137] As used herein, the term “hsa-miR-6787-5p gene” or “hsa-miR-6787-5p” includes the hsa-miR-6787-5p gene described in SEQ ID NO: 12 (miRBase Accession No. MIMAT0027474) and homologs or orthologs in other species. The hsa-miR-6787-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6787-5p,” “hsa-mir-6787” (miRBase Accession No. MI0022632, SEQ ID NO: 237) is known to have a hairpin-like structure.
[0138] As used herein, the term "hsa-miR-4454 gene" or "hsa-miR-4454" includes the hsa-miR-4454 gene described in SEQ ID NO: 13 (miRBase Accession No. MIMAT0018976) and homologs or orthologs in other species. The hsa-miR-4454 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4454," "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 238) is known to have a hairpin-like structure.
[0139] As used herein, the term "hsa-miR-3135b gene" or "hsa-miR-3135b" includes the hsa-miR-3135b gene described in SEQ ID NO: 14 (miRBase Accession No. MIMAT0018985) and homologs or orthologs in other species. The hsa-miR-3135b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-3135b," "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 239) is known to have a hairpin-like structure.
[0140] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" includes the hsa-miR-6765-3p gene described in SEQ ID NO: 15 (miRBase Accession No. MIMAT0027431) and homologs or orthologs in other species. The hsa-miR-6765-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6765-3p", "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 240) is known to have a hairpin-like structure.
[0141] As used herein, the term "hsa-miR-7975 gene" or "hsa-miR-7975" includes the hsa-miR-7975 gene described in SEQ ID NO: 16 (miRBase Accession No. MIMAT0031178) and homologs or orthologs in other biological species. The hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online version. In addition, as a precursor of "hsa-miR-7975", "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 241) is known to have a hairpin-like structure.
[0142] As used herein, the term "hsa-miR-204-3p gene" or "hsa-miR-204-3p" includes the hsa-miR-204-3p gene described in SEQ ID NO: 17 (miRBase Accession No. MIMAT0022693) and homologs or orthologs in other species. The hsa-miR-204-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. Furthermore, as a precursor of "hsa-miR-204-3p", "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 242) is known to have a hairpin-like structure.
[0143] As used herein, the term “hsa-miR-7977 gene” or “hsa-miR-7977” includes the hsa-miR-7977 gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0031180) and homologs or orthologs in other biological species. The hsa-miR-7977 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online version. In addition, as a precursor of “hsa-miR-7977”, “hsa-mir-7977” (miRBase Accession No. MI0025753, SEQ ID NO: 243) is known to form a hairpin-like structure.
[0144] As used herein, the term "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" includes the hsa-miR-7110-5p gene described in SEQ ID NO: 19 (miRBase Accession No. MIMAT0028117) and homologs or orthologs in other species. The hsa-miR-7110-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7110-5p", "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 244) is known to have a hairpin-like structure.
[0145] As used herein, the term "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" includes the hsa-miR-6717-5p gene described in SEQ ID NO: 20 (miRBase Accession No. MIMAT0025846) and homologs or orthologs in other species. The hsa-miR-6717-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6717-5p," "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 245) is known to have a hairpin-like structure.
[0146] As used herein, the term "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" includes the hsa-miR-6870-5p gene described in SEQ ID NO: 21 (miRBase Accession No. MIMAT0027640) and homologs or orthologs in other species. The hsa-miR-6870-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6870-5p", "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 246) is known to have a hairpin-like structure.
[0147] As used herein, the term "hsa-miR-663b gene" or "hsa-miR-663b" includes the hsa-miR-663b gene described in SEQ ID NO: 22 (miRBase Accession No. MIMAT0005867) and homologs or orthologs in other species. The hsa-miR-663b gene can be obtained by the method described in Takada S et al., 2008, Leukemia, Vol. 22, pp. 1274-1278. Furthermore, as a precursor of "hsa-miR-663b," "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 247) is known to have a hairpin-like structure.
[0148] As used herein, the term “hsa-miR-6875-5p gene” or “hsa-miR-6875-5p” includes the hsa-miR-6875-5p gene described in SEQ ID NO: 23 (miRBase Accession No. MIMAT0027650) and homologs or orthologs in other species. The hsa-miR-6875-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6875-5p,” “hsa-mir-6875” (miRBase Accession No. MI0022722, SEQ ID NO: 248) is known to have a hairpin-like structure.
[0149] As used herein, the term “hsa-miR-8072 gene” or “hsa-miR-8072” includes the hsa-miR-8072 gene described in SEQ ID NO: 24 (miRBase Accession No. MIMAT0030999) and homologs or orthologs in other species. The hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8072”, “hsa-mir-8072” (miRBase Accession No. MI0025908, SEQ ID NO: 249) is known to have a hairpin-like structure.
[0150] As used herein, the term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" includes the hsa-miR-6816-5p gene described in SEQ ID NO: 25 (miRBase Accession No. MIMAT0027532) and homologs or orthologs in other species. The hsa-miR-6816-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6816-5p", "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 250) is known to have a hairpin-like structure.
[0151] As used herein, the term “hsa-miR-4281 gene” or “hsa-miR-4281” includes the hsa-miR-4281 gene described in SEQ ID NO: 26 (miRBase Accession No. MIMAT0016907) and homologs or orthologs in other species. The hsa-miR-4281 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4281”, “hsa-mir-4281” (miRBase Accession No. MI0015885, SEQ ID NO: 251) is known to have a hairpin-like structure.
[0152] As used herein, the term “hsa-miR-6729-5p gene” or “hsa-miR-6729-5p” includes the hsa-miR-6729-5p gene described in SEQ ID NO: 27 (miRBase Accession No. MIMAT0027359) and homologs or orthologs in other species. The hsa-miR-6729-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6729-5p,” “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 252) is known to have a hairpin-like structure.
[0153] As used herein, the term “hsa-miR-8069 gene” or “hsa-miR-8069” includes the hsa-miR-8069 gene described in SEQ ID NO: 28 (miRBase Accession No. MIMAT0030996) and homologs or orthologs in other species. The hsa-miR-8069 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8069,” “hsa-mir-8069” (miRBase Accession No. MI0025905, SEQ ID NO: 253) is known to have a hairpin-like structure.
[0154] As used herein, the term “hsa-miR-4706 gene” or “hsa-miR-4706” includes the hsa-miR-4706 gene described in SEQ ID NO: 29 (miRBase Accession No. MIMAT0019806) and homologs or orthologs in other species. The hsa-miR-4706 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4706,” “hsa-mir-4706” (miRBase Accession No. MI0017339, SEQ ID NO: 254) is known to have a hairpin-like structure.
[0155] As used herein, the term "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" includes the hsa-miR-7108-5p gene described in SEQ ID NO: 30 (miRBase Accession No. MIMAT0028113) and homologs or orthologs in other species. The hsa-miR-7108-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7108-5p", "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 255) is known to have a hairpin-like structure.
[0156] As used herein, the term “hsa-miR-4433b-3p gene” or “hsa-miR-4433b-3p” includes the hsa-miR-4433b-3p gene described in SEQ ID NO: 31 (miRBase Accession No. MIMAT0030414) and homologs or orthologs in other species. The hsa-miR-4433b-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of “hsa-miR-4433b-3p,” “hsa-mir-4433b” (miRBase Accession No. MI0025511, SEQ ID NO: 256) is known to have a hairpin-like structure.
[0157] As used herein, the term “hsa-miR-6893-5p gene” or “hsa-miR-6893-5p” includes the hsa-miR-6893-5p gene described in SEQ ID NO: 32 (miRBase Accession No. MIMAT0027686) and homologs or orthologs in other species. The hsa-miR-6893-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6893-5p,” “hsa-mir-6893” (miRBase Accession No. MI0022740, SEQ ID NO: 257) is known to have a hairpin-like structure.
[0158] As used herein, the term "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" includes the hsa-miR-6857-5p gene described in SEQ ID NO: 33 (miRBase Accession No. MIMAT0027614) and homologs or orthologs in other species. The hsa-miR-6857-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6857-5p", "hsa-mir-6857" (miRBase Accession No. MI0022703, SEQ ID NO: 258) is known to have a hairpin-like structure.
[0159] As used herein, the term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" includes the hsa-miR-1227-5p gene described in SEQ ID NO: 34 (miRBase Accession No. MIMAT0022941) and homologs or orthologs in other species. The hsa-miR-1227-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1227-5p", "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 259) is known to have a hairpin-like structure.
[0160] As used herein, the term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" includes the hsa-miR-6741-5p gene described in SEQ ID NO: 35 (miRBase Accession No. MIMAT0027383) and homologs or orthologs in other species. The hsa-miR-6741-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6741-5p", "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 260) is known to have a hairpin-like structure.
[0161] As used herein, the term "hsa-miR-451a gene" or "hsa-miR-451a" includes the hsa-miR-451a gene described in SEQ ID NO: 36 (miRBase Accession No. MIMAT0001631) and homologs or orthologs in other species. The hsa-miR-451a gene can be obtained by the method described in Altuvia Y et al., 2005, Nucleic Acids Res, Vol. 33, pp. 2697-2706. Furthermore, as a precursor of "hsa-miR-451a", "hsa-mir-451a" (miRBase Accession No. MI0001729, SEQ ID NO: 261) is known to have a hairpin-like structure.
[0162] As used herein, the term “hsa-miR-8063 gene” or “hsa-miR-8063” includes the hsa-miR-8063 gene described in SEQ ID NO: 37 (miRBase Accession No. MIMAT0030990) and homologs or orthologs in other species. The hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8063”, “hsa-mir-8063” (miRBase Accession No. MI0025899, SEQ ID NO: 262) is known to form a hairpin-like structure.
[0163] As used herein, the term “hsa-miR-3622a-5p gene” or “hsa-miR-3622a-5p” includes the hsa-miR-3622a-5p gene described in SEQ ID NO: 38 (miRBase Accession No. MIMAT0018003) and homologs or orthologs in other biological species. The hsa-miR-3622a-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of “hsa-miR-3622a-5p,” “hsa-mir-3622a” (miRBase Accession No. MI0016013, SEQ ID NO: 263) is known to have a hairpin-like structure.
[0164] As used herein, the term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" includes the hsa-miR-615-5p gene described in SEQ ID NO: 39 (miRBase Accession No. MIMAT0004804) and homologs or orthologs in other species. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-615-5p", "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 264) is known to have a hairpin-like structure.
[0165] As used herein, the term "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" includes the hsa-miR-128-1-5p gene described in SEQ ID NO: 40 (miRBase Accession No. MIMAT0026477) and homologs or orthologs in other species. The hsa-miR-128-1-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-128-1-5p," "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 265) is known to have a hairpin-like structure.
[0166] As used herein, the term "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" includes the hsa-miR-6825-5p gene described in SEQ ID NO: 41 (miRBase Accession No. MIMAT0027550) and homologs or orthologs in other species. The hsa-miR-6825-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6825-5p", "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 266) is known to have a hairpin-like structure.
[0167] As used herein, the term “hsa-miR-1260b gene” or “hsa-miR-1260b” includes the hsa-miR-1260b gene described in SEQ ID NO: 42 (miRBase Accession No. MIMAT0015041) and homologs or orthologs in other species. The hsa-miR-1260b gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, as a precursor of “hsa-miR-1260b”, “hsa-mir-1260b” (miRBase Accession No. MI0014197, SEQ ID NO: 267) is known to have a hairpin-like structure.
[0168] As used herein, the term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" includes the hsa-miR-4433-3p gene described in SEQ ID NO: 43 (miRBase Accession No. MIMAT0018949) and homologs or orthologs in other species. The hsa-miR-4433-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4433-3p", "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 268) is known to have a hairpin-like structure.
[0169] As used herein, the term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" includes the hsa-miR-4665-5p gene described in SEQ ID NO: 44 (miRBase Accession No. MIMAT0019739) and homologs or orthologs in other species. The hsa-miR-4665-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4665-5p", "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 269) is known to have a hairpin-like structure.
[0170] As used herein, the term "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" includes the hsa-miR-7845-5p gene described in SEQ ID NO: 45 (miRBase Accession No. MIMAT0030420) and homologs or orthologs in other species. The hsa-miR-7845-5p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of "hsa-miR-7845-5p", "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 270) is known to have a hairpin-like structure.
[0171] As used herein, the term “hsa-miR-1908-5p gene” or “hsa-miR-1908-5p” includes the hsa-miR-1908-5p gene described in SEQ ID NO: 46 (miRBase Accession No. MIMAT0007881) and homologs or orthologs in other biological species. The hsa-miR-1908-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, as a precursor of “hsa-miR-1908-5p”, “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 271) is known to have a hairpin-like structure.
[0172] As used herein, the term "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" includes the hsa-miR-6840-3p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0027583) and homologs or orthologs in other species. The hsa-miR-6840-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6840-3p", "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 272) is known to have a hairpin-like structure.
[0173] As used herein, the term "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" includes the hsa-miR-6765-5p gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0027430) and homologs or orthologs in other species. The hsa-miR-6765-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6765-5p", "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 240) is known to have a hairpin-like structure.
[0174] As used herein, the term “hsa-miR-296-5p gene” or “hsa-miR-296-5p” includes the hsa-miR-296-5p gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0000690) and homologs or orthologs in other species. The hsa-miR-296-5p gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Furthermore, as a precursor of “hsa-miR-296-5p,” “hsa-mir-296” (miRBase Accession No. MI0000747, SEQ ID NO: 273) is known to have a hairpin-like structure.
[0175] As used herein, the term "hsa-miR-3675-3p gene" or "hsa-miR-3675-3p" includes the hsa-miR-3675-3p gene described in SEQ ID NO: 50 (miRBase Accession No. MIMAT0018099) and homologs or orthologs in other species. The hsa-miR-3675-3p gene can be obtained by the method described in Vaz C et al., 2010, BMC Genomics, Vol. 11, p288. Furthermore, as a precursor of "hsa-miR-3675-3p", "hsa-mir-3675" (miRBase Accession No. MI0016076, SEQ ID NO: 274) is known to have a hairpin-like structure.
[0176] As used herein, the term “hsa-miR-6781-5p gene” or “hsa-miR-6781-5p” includes the hsa-miR-6781-5p gene described in SEQ ID NO: 51 (miRBase Accession No. MIMAT0027462) and homologs or orthologs in other species. The hsa-miR-6781-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6781-5p,” “hsa-mir-6781” (miRBase Accession No. MI0022626, SEQ ID NO: 275) is known to have a hairpin-like structure.
[0177] As used herein, the term “hsa-miR-423-5p gene” or “hsa-miR-423-5p” includes the hsa-miR-423-5p gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0004748) and homologs or orthologs in other biological species. The hsa-miR-423-5p gene can be obtained by the method described in Kasashima K et al., 2004, Biochem Biophys Res Commun, Vol. 322, pp. 403-410. In addition, as a precursor of “hsa-miR-423-5p”, “hsa-mir-423” (miRBase Accession No. MI0001445, SEQ ID NO: 276) is known to have a hairpin-like structure.
[0178] As used herein, the term "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" includes the hsa-miR-3663-3p gene described in SEQ ID NO: 53 (miRBase Accession No. MIMAT0018085) and homologs or orthologs in other species. The hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3663-3p", "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 277) is known to have a hairpin-like structure.
[0179] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" includes the hsa-miR-6784-5p gene described in SEQ ID NO: 54 (miRBase Accession No. MIMAT0027468) and homologs or orthologs in other species. The hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6784-5p", "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 278) is known to have a hairpin-like structure.
[0180] As used herein, the term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" includes the hsa-miR-6749-5p gene described in SEQ ID NO: 55 (miRBase Accession No. MIMAT0027398) and homologs or orthologs in other species. The hsa-miR-6749-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6749-5p", "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 279) is known to have a hairpin-like structure.
[0181] As used herein, the term "hsa-miR-1231 gene" or "hsa-miR-1231" includes the hsa-miR-1231 gene described in SEQ ID NO: 56 (miRBase Accession No. MIMAT0005586) and homologs or orthologs in other species. The hsa-miR-1231 gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1231," "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 280) is known to have a hairpin-like structure.
[0182] As used herein, the term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" includes the hsa-miR-4746-3p gene described in SEQ ID NO: 57 (miRBase Accession No. MIMAT0019881) and homologs or orthologs in other species. The hsa-miR-4746-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4746-3p", "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 281) is known to have a hairpin-like structure.
[0183] As used herein, the term “hsa-miR-6780b-5p gene” or “hsa-miR-6780b-5p” includes the hsa-miR-6780b-5p gene described in SEQ ID NO: 58 (miRBase Accession No. MIMAT0027572) and homologs or orthologs in other species. The hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6780b-5p,” “hsa-mir-6780b” (miRBase Accession No. MI0022681, SEQ ID NO: 282) is known to have a hairpin-like structure.
[0184] As used herein, the term "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" includes the hsa-miR-4758-5p gene described in SEQ ID NO: 59 (miRBase Accession No. MIMAT0019903) and homologs or orthologs in other species. The hsa-miR-4758-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4758-5p", "hsa-mir-4758" (miRBase Accession No. MI0017399, SEQ ID NO: 283) is known to have a hairpin-like structure.
[0185] As used herein, the term "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" includes the hsa-miR-3679-5p gene described in SEQ ID NO: 60 (miRBase Accession No. MIMAT0018104) and homologs or orthologs in other species. The hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of "hsa-miR-3679-5p," "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 236) is known to have a hairpin-like structure.
[0186] As used herein, the term “hsa-miR-3184-5p gene” or “hsa-miR-3184-5p” includes the hsa-miR-3184-5p gene described in SEQ ID NO: 61 (miRBase Accession No. MIMAT0015064) and homologs or orthologs in other species. The hsa-miR-3184-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3184-5p,” “hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 284) is known to have a hairpin-like structure.
[0187] As used herein, the term “hsa-miR-6125 gene” or “hsa-miR-6125” includes the hsa-miR-6125 gene described in SEQ ID NO: 62 (miRBase Accession No. MIMAT0024598) and homologs or orthologs in other species. The hsa-miR-6125 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of “hsa-miR-6125,” “hsa-mir-6125” (miRBase Accession No. MI0021259, SEQ ID NO: 285) is known to have a hairpin-like structure.
[0188] As used herein, the term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" includes the hsa-miR-6721-5p gene described in SEQ ID NO: 63 (miRBase Accession No. MIMAT0025852) and homologs or orthologs in other species. The hsa-miR-6721-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6721-5p," "hsa-mir-6721" (miRBase Accession No. MI0022556, SEQ ID NO: 286) is known to have a hairpin-like structure.
[0189] As used herein, the term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" includes the hsa-miR-6791-5p gene described in SEQ ID NO: 64 (miRBase Accession No. MIMAT0027482) and homologs or orthologs in other species. The hsa-miR-6791-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6791-5p", "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 287) is known to have a hairpin-like structure.
[0190] As used herein, the term “hsa-miR-3185 gene” or “hsa-miR-3185” includes the hsa-miR-3185 gene described in SEQ ID NO: 65 (miRBase Accession No. MIMAT0015065) and homologs or orthologs in other species. The hsa-miR-3185 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3185,” “hsa-mir-3185” (miRBase Accession No. MI0014227, SEQ ID NO: 288) is known to have a hairpin-like structure.
[0191] As used herein, the term “hsa-miR-1260a gene” or “hsa-miR-1260a” includes the hsa-miR-1260a gene described in SEQ ID NO: 66 (miRBase Accession No. MIMAT0005911) and homologs or orthologs in other biological species. The hsa-miR-1260a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1260a”, “hsa-mir-1260a” (miRBase Accession No. MI0006394, SEQ ID NO: 289) is known to have a hairpin-like structure.
[0192] As used herein, the term “hsa-miR-3197 gene” or “hsa-miR-3197” includes the hsa-miR-3197 gene described in SEQ ID NO: 67 (miRBase Accession No. MIMAT0015082) and homologs or orthologs in other species. The hsa-miR-3197 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3197,” “hsa-mir-3197” (miRBase Accession No. MI0014245, SEQ ID NO: 290) is known to have a hairpin-like structure.
[0193] As used herein, the term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" includes the hsa-miR-6845-5p gene described in SEQ ID NO: 68 (miRBase Accession No. MIMAT0027590) and homologs or orthologs in other species. The hsa-miR-6845-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6845-5p", "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 291) is known to have a hairpin-like structure.
[0194] As used herein, the term “hsa-miR-6887-5p gene” or “hsa-miR-6887-5p” includes the hsa-miR-6887-5p gene described in SEQ ID NO: 69 (miRBase Accession No. MIMAT0027674) and homologs or orthologs in other species. The hsa-miR-6887-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6887-5p,” “hsa-mir-6887” (miRBase Accession No. MI0022734, SEQ ID NO: 292) is known to have a hairpin-like structure.
[0195] As used herein, the term "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" includes the hsa-miR-6738-5p gene described in SEQ ID NO: 70 (miRBase Accession No. MIMAT0027377) and homologs or orthologs in other species. The hsa-miR-6738-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6738-5p", "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 293) is known to have a hairpin-like structure.
[0196] As used herein, the term “hsa-miR-6872-3p gene” or “hsa-miR-6872-3p” includes the hsa-miR-6872-3p gene described in SEQ ID NO: 71 (miRBase Accession No. MIMAT0027645) and homologs or orthologs in other species. The hsa-miR-6872-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6872-3p,” “hsa-mir-6872” (miRBase Accession No. MI0022719, SEQ ID NO: 294) is known to have a hairpin-like structure.
[0197] As used herein, the term "hsa-miR-4497 gene" or "hsa-miR-4497" includes the hsa-miR-4497 gene described in SEQ ID NO: 72 (miRBase Accession No. MIMAT0019032) and homologs or orthologs in other species. The hsa-miR-4497 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4497", "hsa-mir-4497" (miRBase Accession No. MI0016859, SEQ ID NO: 295) is known to have a hairpin-like structure.
[0198] As used herein, the term "hsa-miR-1229-5p gene" or "hsa-miR-1229-5p" includes the hsa-miR-1229-5p gene described in SEQ ID NO: 73 (miRBase Accession No. MIMAT0022942) and homologs or orthologs in other biological species. The hsa-miR-1229-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1229-5p", "hsa-mir-1229" (miRBase Accession No. MI0006319, SEQ ID NO: 296) is known to have a hairpin-like structure.
[0199] As used herein, the term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" includes the hsa-miR-6820-5p gene described in SEQ ID NO: 74 (miRBase Accession No. MIMAT0027540) and homologs or orthologs in other species. The hsa-miR-6820-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6820-5p", "hsa-mir-6820" (miRBase Accession No. MI0022665, SEQ ID NO: 297) is known to have a hairpin-like structure.
[0200] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" includes the hsa-miR-6777-5p gene described in SEQ ID NO: 75 (miRBase Accession No. MIMAT0027454) and homologs or orthologs in other species. The hsa-miR-6777-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6777-5p", "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 298) is known to have a hairpin-like structure.
[0201] As used herein, the term “hsa-miR-3917 gene” or “hsa-miR-3917” includes the hsa-miR-3917 gene described in SEQ ID NO: 76 (miRBase Accession No. MIMAT0018191) and homologs or orthologs in other species. The hsa-miR-3917 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of “hsa-miR-3917,” “hsa-mir-3917” (miRBase Accession No. MI0016423, SEQ ID NO: 299) is known to have a hairpin-like structure.
[0202] As used herein, the term “hsa-miR-5787 gene” or “hsa-miR-5787” includes the hsa-miR-5787 gene described in SEQ ID NO: 77 (miRBase Accession No. MIMAT0023252) and homologs or orthologs in other species. The hsa-miR-5787 gene can be obtained by the method described in Yoo H et al., 2011, Biochem Biophys Res Commun, Vol. 415, pp. 567-572. Furthermore, as a precursor of “hsa-miR-5787,” “hsa-mir-5787” (miRBase Accession No. MI0019797, SEQ ID NO: 300) is known to have a hairpin-like structure.
[0203] As used herein, the term “hsa-miR-4286 gene” or “hsa-miR-4286” includes the hsa-miR-4286 gene described in SEQ ID NO: 78 (miRBase Accession No. MIMAT0016916) and homologs or orthologs in other biological species. The hsa-miR-4286 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4286”, “hsa-mir-4286” (miRBase Accession No. MI0015894, SEQ ID NO: 301) is known to have a hairpin-like structure.
[0204] As used herein, the term “hsa-miR-6877-5p gene” or “hsa-miR-6877-5p” includes the hsa-miR-6877-5p gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0027654) and homologs or orthologs in other species. The hsa-miR-6877-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6877-5p,” “hsa-mir-6877” (miRBase Accession No. MI0022724, SEQ ID NO: 302) is known to have a hairpin-like structure.
[0205] As used herein, the term "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" includes the hsa-miR-1225-3p gene described in SEQ ID NO: 80 (miRBase Accession No. MIMAT0005573) and homologs or orthologs in other species. The hsa-miR-1225-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1225-3p", "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 303) is known to have a hairpin-like structure.
[0206] As used herein, the term “hsa-miR-6088 gene” or “hsa-miR-6088” includes the hsa-miR-6088 gene described in SEQ ID NO: 81 (miRBase Accession No. MIMAT0023713) and homologs or orthologs in other species. The hsa-miR-6088 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor of “hsa-miR-6088,” “hsa-mir-6088” (miRBase Accession No. MI0020365, SEQ ID NO: 304) is known to have a hairpin-like structure.
[0207] As used herein, the term "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" includes the hsa-miR-6800-5p gene described in SEQ ID NO: 82 (miRBase Accession No. MIMAT0027500) and homologs or orthologs in other species. The hsa-miR-6800-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6800-5p", "hsa-mir-6800" (miRBase Accession No. MI0022645, SEQ ID NO: 305) is known to have a hairpin-like structure.
[0208] As used herein, the term “hsa-miR-1246 gene” or “hsa-miR-1246” includes the hsa-miR-1246 gene described in SEQ ID NO: 83 (miRBase Accession No. MIMAT0005898) and homologs or orthologs in other biological species. The hsa-miR-1246 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1246”, “hsa-mir-1246” (miRBase Accession No. MI0006381, SEQ ID NO: 306) is known to have a hairpin-like structure.
[0209] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" includes the hsa-miR-4467 gene described in SEQ ID NO: 84 (miRBase Accession No. MIMAT0018994) and homologs or orthologs in other species. The hsa-miR-4467 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4467", "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 307) is known to have a hairpin-like structure.
[0210] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" includes the hsa-miR-4419b gene described in SEQ ID NO: 85 (miRBase Accession No. MIMAT0019034) and homologs or orthologs in other species. The hsa-miR-4419b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4419b", "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 308) is known to have a hairpin-like structure.
[0211] As used herein, the term "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" includes the hsa-miR-1914-3p gene described in SEQ ID NO: 86 (miRBase Accession No. MIMAT0007890) and homologs or orthologs in other biological species. The hsa-miR-1914-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of "hsa-miR-1914-3p", "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 309) is known to have a hairpin-like structure.
[0212] As used herein, the term "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" includes the hsa-miR-4632-5p gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0022977) and homologs or orthologs in other species. The hsa-miR-4632-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4632-5p", "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 310) is known to have a hairpin-like structure.
[0213] As used herein, the term “hsa-miR-1915-5p gene” or “hsa-miR-1915-5p” includes the hsa-miR-1915-5p gene described in SEQ ID NO: 88 (miRBase Accession No. MIMAT0007891) and homologs or orthologs in other biological species. The hsa-miR-1915-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of “hsa-miR-1915-5p,” “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 311) is known to have a hairpin-like structure.
[0214] As used herein, the term "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" includes the hsa-miR-3940-5p gene described in SEQ ID NO: 89 (miRBase Accession No. MIMAT0019229) and homologs or orthologs in other species. The hsa-miR-3940-5p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3940-5p," "hsa-mir-3940" (miRBase Accession No. MI0016597, SEQ ID NO: 312) is known to have a hairpin-like structure.
[0215] As used herein, the term "hsa-miR-1185-2-3p gene" or "hsa-miR-1185-2-3p" includes the hsa-miR-1185-2-3p gene described in SEQ ID NO: 90 (miRBase Accession No. MIMAT0022713) and homologs or orthologs in other species. The hsa-miR-1185-2-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-1185-2-3p", "hsa-mir-1185-2" (miRBase Accession No. MI0003821, SEQ ID NO: 313) is known to have a hairpin-like structure.
[0216] As used herein, the term "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" includes the hsa-miR-6746-5p gene described in SEQ ID NO: 91 (miRBase Accession No. MIMAT0027392) and homologs or orthologs in other species. The hsa-miR-6746-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6746-5p", "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 314) is known to have a hairpin-like structure.
[0217] As used herein, the term "hsa-miR-5001-5p gene" or "hsa-miR-5001-5p" includes the hsa-miR-5001-5p gene described in SEQ ID NO: 92 (miRBase Accession No. MIMAT0021021) and homologs or orthologs in other biological species. The hsa-miR-5001-5p gene can be obtained by the method described in Hansen TB et al., 2011, RNA Biol, Vol. 8, pp. 378-383. Furthermore, as a precursor of "hsa-miR-5001-5p," "hsa-mir-5001" (miRBase Accession No. MI0017867, SEQ ID NO: 315) is known to have a hairpin-like structure.
[0218] As used herein, the term "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" includes the hsa-miR-1228-5p gene described in SEQ ID NO: 93 (miRBase Accession No. MIMAT0005582) and homologs or orthologs in other species. The hsa-miR-1228-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1228-5p", "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 316) is known to have a hairpin-like structure.
[0219] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" includes the hsa-miR-5572 gene described in SEQ ID NO: 94 (miRBase Accession No. MIMAT0022260) and homologs or orthologs in other species. The hsa-miR-5572 gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. In addition, as a precursor of "hsa-miR-5572", "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 317) is known to have a hairpin-like structure.
[0220] As used herein, the term “hsa-miR-4327 gene” or “hsa-miR-4327” includes the hsa-miR-4327 gene described in SEQ ID NO: 95 (miRBase Accession No. MIMAT0016889) and homologs or orthologs in other species. The hsa-miR-4327 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4327”, “hsa-mir-4327” (miRBase Accession No. MI0015867, SEQ ID NO: 318) is known to have a hairpin-like structure.
[0221] As used herein, the term "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" includes the hsa-miR-4638-5p gene described in SEQ ID NO: 96 (miRBase Accession No. MIMAT0019695) and homologs or orthologs in other species. The hsa-miR-4638-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4638-5p", "hsa-mir-4638" (miRBase Accession No. MI0017265, SEQ ID NO: 319) is known to have a hairpin-like structure.
[0222] As used herein, the term “hsa-miR-6799-5p gene” or “hsa-miR-6799-5p” includes the hsa-miR-6799-5p gene described in SEQ ID NO: 97 (miRBase Accession No. MIMAT0027498) and homologs or orthologs in other species. The hsa-miR-6799-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6799-5p,” “hsa-mir-6799” (miRBase Accession No. MI0022644, SEQ ID NO: 320) is known to have a hairpin-like structure.
[0223] As used herein, the term "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" includes the hsa-miR-6861-5p gene described in SEQ ID NO: 98 (miRBase Accession No. MIMAT0027623) and homologs or orthologs in other species. The hsa-miR-6861-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6861-5p", "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 321) is known to have a hairpin-like structure.
[0224] As used herein, the term "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" includes the hsa-miR-6727-5p gene described in SEQ ID NO: 99 (miRBase Accession No. MIMAT0027355) and homologs or orthologs in other species. The hsa-miR-6727-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6727-5p", "hsa-mir-6727" (miRBase Accession No. MI0022572, SEQ ID NO: 322) is known to have a hairpin-like structure.
[0225] As used herein, the term "hsa-miR-4513 gene" or "hsa-miR-4513" includes the hsa-miR-4513 gene described in SEQ ID NO: 100 (miRBase Accession No. MIMAT0019050) and homologs or orthologs in other species. The hsa-miR-4513 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4513," "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 323) is known to have a hairpin-like structure.
[0226] As used herein, the term "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" includes the hsa-miR-6805-3p gene described in SEQ ID NO: 101 (miRBase Accession No. MIMAT0027511) and homologs or orthologs in other species. The hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6805-3p", "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 324) is known to have a hairpin-like structure.
[0227] As used herein, the term "hsa-miR-6808-5p gene" or "hsa-miR-6808-5p" includes the hsa-miR-6808-5p gene described in SEQ ID NO: 102 (miRBase Accession No. MIMAT0027516) and homologs or orthologs in other species. The hsa-miR-6808-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6808-5p", "hsa-mir-6808" (miRBase Accession No. MI0022653, SEQ ID NO: 325) is known to have a hairpin-like structure.
[0228] As used herein, the term "hsa-miR-4449 gene" or "hsa-miR-4449" includes the hsa-miR-4449 gene described in SEQ ID NO: 103 (miRBase Accession No. MIMAT0018968) and homologs or orthologs in other species. The hsa-miR-4449 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4449", "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 326) is known to have a hairpin-like structure.
[0229] As used herein, the term “hsa-miR-1199-5p gene” or “hsa-miR-1199-5p” includes the hsa-miR-1199-5p gene described in SEQ ID NO: 104 (miRBase Accession No. MIMAT0031119) and homologs or orthologs in other species. The hsa-miR-1199-5p gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, Vol. 42, pp. 391-402. Furthermore, as a precursor of “hsa-miR-1199-5p,” “hsa-mir-1199” (miRBase Accession No. MI0020340, SEQ ID NO: 327) is known to have a hairpin-like structure.
[0230] As used herein, the term “hsa-miR-1275 gene” or “hsa-miR-1275” includes the hsa-miR-1275 gene described in SEQ ID NO: 105 (miRBase Accession No. MIMAT0005929) and homologs or orthologs in other biological species. The hsa-miR-1275 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1275”, “hsa-mir-1275” (miRBase Accession No. MI0006415, SEQ ID NO: 328) is known to have a hairpin-like structure.
[0231] As used herein, the term “hsa-miR-4792 gene” or “hsa-miR-4792” includes the hsa-miR-4792 gene described in SEQ ID NO: 106 (miRBase Accession No. MIMAT0019964) and homologs or orthologs in other species. The hsa-miR-4792 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, as a precursor of “hsa-miR-4792”, “hsa-mir-4792” (miRBase Accession No. MI0017439, SEQ ID NO: 329) is known to have a hairpin-like structure.
[0232] As used herein, the term "hsa-miR-4443 gene" or "hsa-miR-4443" includes the hsa-miR-4443 gene described in SEQ ID NO: 107 (miRBase Accession No. MIMAT0018961) and homologs or orthologs in other species. The hsa-miR-4443 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4443", "hsa-mir-4443" (miRBase Accession No. MI0016786, SEQ ID NO: 330) is known to have a hairpin-like structure.
[0233] As used herein, the term "hsa-miR-6891-5p gene" or "hsa-miR-6891-5p" includes the hsa-miR-6891-5p gene described in SEQ ID NO: 108 (miRBase Accession No. MIMAT0027682) and homologs or orthologs in other biological species. The hsa-miR-6891-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6891-5p", "hsa-mir-6891" (miRBase Accession No. MI0022738, SEQ ID NO: 331) is known to have a hairpin-like structure.
[0234] As used herein, the term "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" includes the hsa-miR-6826-5p gene described in SEQ ID NO: 109 (miRBase Accession No. MIMAT0027552) and homologs or orthologs in other species. The hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6826-5p," "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 332) is known to have a hairpin-like structure.
[0235] As used herein, the term "hsa-miR-6807-5p gene" or "hsa-miR-6807-5p" includes the hsa-miR-6807-5p gene described in SEQ ID NO: 110 (miRBase Accession No. MIMAT0027514) and homologs or orthologs in other species. The hsa-miR-6807-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6807-5p", "hsa-mir-6807" (miRBase Accession No. MI0022652, SEQ ID NO: 333) is known to have a hairpin-like structure.
[0236] As used herein, the term “hsa-miR-7150 gene” or “hsa-miR-7150” includes the hsa-miR-7150 gene described in SEQ ID NO: 111 (miRBase Accession No. MIMAT0028211) and homologs or orthologs in other species. The hsa-miR-7150 gene can be obtained by the method described in Oulas A et al., 2009, Nucleic Acids Res, Vol. 37, pp. 3276-3287. In addition, as a precursor of “hsa-miR-7150”, “hsa-mir-7150” (miRBase Accession No. MI0023610, SEQ ID NO: 334) is known to have a hairpin-like structure.
[0237] As used herein, the term "hsa-miR-4534 gene" or "hsa-miR-4534" includes the hsa-miR-4534 gene described in SEQ ID NO: 112 (miRBase Accession No. MIMAT0019073) as well as homologs or orthologs in other species. The hsa-miR-4534 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4534," "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 335) is known to have a hairpin-like structure.
[0238] As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" includes the hsa-miR-4476 gene described in SEQ ID NO: 113 (miRBase Accession No. MIMAT0019003) and homologs or orthologs in other species. The hsa-miR-4476 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4476", "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 336) is known to have a hairpin-like structure.
[0239] As used herein, the term "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" includes the hsa-miR-4649-5p gene described in SEQ ID NO: 114 (miRBase Accession No. MIMAT0019711) and homologs or orthologs in other species. The hsa-miR-4649-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4649-5p", "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 337) is known to have a hairpin-like structure.
[0240] As used herein, the term "hsa-miR-4525 gene" or "hsa-miR-4525" includes the hsa-miR-4525 gene described in SEQ ID NO: 115 (miRBase Accession No. MIMAT0019064) and homologs or orthologs in other species. The hsa-miR-4525 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4525," "hsa-mir-4525" (miRBase Accession No. MI0016892, SEQ ID NO: 338) is known to have a hairpin-like structure.
[0241] As used herein, the term "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" includes the hsa-miR-1915-3p gene described in SEQ ID NO: 116 (miRBase Accession No. MIMAT0007892) and homologs or orthologs in other biological species. The hsa-miR-1915-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor of "hsa-miR-1915-3p", "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 311) is known to have a hairpin-like structure.
[0242] As used herein, the term "hsa-miR-4516 gene" or "hsa-miR-4516" includes the hsa-miR-4516 gene described in SEQ ID NO: 117 (miRBase Accession No. MIMAT0019053) and homologs or orthologs in other species. The hsa-miR-4516 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4516," "hsa-mir-4516" (miRBase Accession No. MI0016882, SEQ ID NO: 339) is known to have a hairpin-like structure.
[0243] As used herein, the term "hsa-miR-4417 gene" or "hsa-miR-4417" includes the hsa-miR-4417 gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0018929) and homologs or orthologs in other species. The hsa-miR-4417 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4417," "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 340) is known to have a hairpin-like structure.
[0244] As used herein, the term “hsa-miR-642b-3p gene” or “hsa-miR-642b-3p” includes the hsa-miR-642b-3p gene described in SEQ ID NO: 119 (miRBase Accession No. MIMAT0018444) and homologs or orthologs in other biological species. The hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of “hsa-miR-642b-3p,” “hsa-mir-642b” (miRBase Accession No. MI0016685, SEQ ID NO: 341) is known to have a hairpin-like structure.
[0245] As used herein, the term “hsa-miR-3141 gene” or “hsa-miR-3141” includes the hsa-miR-3141 gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0015010) and homologs or orthologs in other species. The hsa-miR-3141 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3141,” “hsa-mir-3141” (miRBase Accession No. MI0014165, SEQ ID NO: 342) is known to have a hairpin-like structure.
[0246] As used herein, the term "hsa-miR-5100 gene" or "hsa-miR-5100" includes the hsa-miR-5100 gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0022259) and homologs or orthologs in other species. The hsa-miR-5100 gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis, Vol. 18, pp. 127-131. In addition, as a precursor of "hsa-miR-5100", "hsa-mir-5100" (miRBase Accession No. MI0019116, SEQ ID NO: 343) is known to have a hairpin-like structure.
[0247] As used herein, the term "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" includes the hsa-miR-6848-5p gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0027596) and homologs or orthologs in other species. The hsa-miR-6848-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6848-5p," "hsa-mir-6848" (miRBase Accession No. MI0022694, SEQ ID NO: 344) is known to have a hairpin-like structure.
[0248] As used herein, the term “hsa-miR-4739 gene” or “hsa-miR-4739” includes the hsa-miR-4739 gene described in SEQ ID NO: 123 (miRBase Accession No. MIMAT0019868) and homologs or orthologs in other species. The hsa-miR-4739 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. In addition, as a precursor of “hsa-miR-4739”, “hsa-mir-4739” (miRBase Accession No. MI0017377, SEQ ID NO: 345) is known to have a hairpin-like structure.
[0249] As used herein, the term "hsa-miR-4459 gene" or "hsa-miR-4459" includes the hsa-miR-4459 gene described in SEQ ID NO: 124 (miRBase Accession No. MIMAT0018981) and homologs or orthologs in other species. The hsa-miR-4459 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4459", "hsa-mir-4459" (miRBase Accession No. MI0016805, SEQ ID NO: 346) is known to have a hairpin-like structure.
[0250] As used herein, the term "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" includes the hsa-miR-1237-5p gene described in SEQ ID NO: 125 (miRBase Accession No. MIMAT0022946) and homologs or orthologs in other species. The hsa-miR-1237-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1237-5p", "hsa-mir-1237" (miRBase Accession No. MI0006327, SEQ ID NO: 347) is known to have a hairpin-like structure.
[0251] As used herein, the term “hsa-miR-296-3p gene” or “hsa-miR-296-3p” includes the hsa-miR-296-3p gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0004679) and homologs or orthologs in other species. The hsa-miR-296-3p gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Furthermore, as a precursor of “hsa-miR-296-3p,” “hsa-mir-296” (miRBase Accession No. MI0000747, SEQ ID NO: 273) is known to have a hairpin-like structure.
[0252] As used herein, the term "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" includes the hsa-miR-4665-3p gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0019740) and homologs or orthologs in other species. The hsa-miR-4665-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4665-3p", "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 269) is known to have a hairpin-like structure.
[0253] As used herein, the term "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" includes the hsa-miR-6786-5p gene described in SEQ ID NO: 128 (miRBase Accession No. MIMAT0027472) and homologs or orthologs in other species. The hsa-miR-6786-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6786-5p", "hsa-mir-6786" (miRBase Accession No. MI0022631, SEQ ID NO: 348) is known to have a hairpin-like structure.
[0254] As used herein, the term “hsa-miR-4258 gene” or “hsa-miR-4258” includes the hsa-miR-4258 gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0016879) and homologs or orthologs in other species. The hsa-miR-4258 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4258”, “hsa-mir-4258” (miRBase Accession No. MI0015857, SEQ ID NO: 349) is known to have a hairpin-like structure.
[0255] As used herein, the term "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" includes the hsa-miR-6510-5p gene described in SEQ ID NO: 130 (miRBase Accession No. MIMAT0025476) and homologs or orthologs in other species. The hsa-miR-6510-5p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, Vol. 20, pp. 4025-4040. Furthermore, as a precursor of "hsa-miR-6510-5p", "hsa-mir-6510" (miRBase Accession No. MI0022222, SEQ ID NO: 350) is known to have a hairpin-like structure.
[0256] As used herein, the term "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" includes the hsa-miR-1343-5p gene described in SEQ ID NO: 131 (miRBase Accession No. MIMAT0027038) and homologs or orthologs in other species. The hsa-miR-1343-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-1343-5p", "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 225) is known to have a hairpin-like structure.
[0257] As used herein, the term “hsa-miR-1247-3p gene” or “hsa-miR-1247-3p” includes the hsa-miR-1247-3p gene described in SEQ ID NO: 132 (miRBase Accession No. MIMAT0022721) and homologs or orthologs in other biological species. The hsa-miR-1247-3p gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, Vol. 18, pp. 610-621. In addition, as a precursor of “hsa-miR-1247-3p”, “hsa-mir-1247” (miRBase Accession No. MI0006382, SEQ ID NO: 351) is known to have a hairpin-like structure.
[0258] As used herein, the term "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" includes the hsa-miR-6805-5p gene described in SEQ ID NO: 133 (miRBase Accession No. MIMAT0027510) and homologs or orthologs in other species. The hsa-miR-6805-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6805-5p", "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 324) is known to have a hairpin-like structure.
[0259] As used herein, the term "hsa-miR-4492 gene" or "hsa-miR-4492" includes the hsa-miR-4492 gene described in SEQ ID NO: 134 (miRBase Accession No. MIMAT0019027) and homologs or orthologs in other species. The hsa-miR-4492 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4492", "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 352) is known to have a hairpin-like structure.
[0260] As used herein, the term “hsa-miR-1469 gene” or “hsa-miR-1469” includes the hsa-miR-1469 gene described in SEQ ID NO: 135 (miRBase Accession No. MIMAT0007347) and homologs or orthologs in other biological species. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p157. In addition, as a precursor of “hsa-miR-1469”, “hsa-mir-1469” (miRBase Accession No. MI0007074, SEQ ID NO: 353) that forms a hairpin-like structure is known.
[0261] As used herein, the term "hsa-miR-1268b gene" or "hsa-miR-1268b" includes the hsa-miR-1268b gene described in SEQ ID NO: 136 (miRBase Accession No. MIMAT0018925) and homologs or orthologs in other species. The hsa-miR-1268b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-1268b", "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 354) is known to have a hairpin-like structure.
[0262] As used herein, the term "hsa-miR-6858-5p gene" or "hsa-miR-6858-5p" includes the hsa-miR-6858-5p gene described in SEQ ID NO: 137 (miRBase Accession No. MIMAT0027616) and homologs or orthologs in other species. The hsa-miR-6858-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6858-5p", "hsa-mir-6858" (miRBase Accession No. MI0022704, SEQ ID NO: 355) is known to have a hairpin-like structure.
[0263] As used herein, the term "hsa-miR-3937 gene" or "hsa-miR-3937" includes the hsa-miR-3937 gene described in SEQ ID NO: 138 (miRBase Accession No. MIMAT0018352) and homologs or orthologs in other species. The hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. Furthermore, as a precursor of "hsa-miR-3937," "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 356) is known to have a hairpin-like structure.
[0264] As used herein, the term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" includes the hsa-miR-939-5p gene described in SEQ ID NO: 139 (miRBase Accession No. MIMAT0004982) and homologs or orthologs in other species. The hsa-miR-939-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, Vol. 67, pp. 6031-6043. Furthermore, as a precursor of "hsa-miR-939-5p", "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 357) is known to have a hairpin-like structure.
[0265] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" includes the hsa-miR-3656 gene described in SEQ ID NO: 140 (miRBase Accession No. MIMAT0018076) and homologs or orthologs in other species. The hsa-miR-3656 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Furthermore, as a precursor of "hsa-miR-3656", "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 358) is known to have a hairpin-like structure.
[0266] As used herein, the term "hsa-miR-744-5p gene" or "hsa-miR-744-5p" includes the hsa-miR-744-5p gene described in SEQ ID NO: 141 (miRBase Accession No. MIMAT0004945) and homologs or orthologs in other species. The hsa-miR-744-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-744-5p", "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 359) is known to have a hairpin-like structure.
[0267] As used herein, the term "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" includes the hsa-miR-4687-3p gene described in SEQ ID NO: 142 (miRBase Accession No. MIMAT0019775) and homologs or orthologs in other species. The hsa-miR-4687-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4687-3p", "hsa-mir-4687" (miRBase Accession No. MI0017319, SEQ ID NO: 360) is known to have a hairpin-like structure.
[0268] As used herein, the term "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" includes the hsa-miR-4763-3p gene described in SEQ ID NO: 143 (miRBase Accession No. MIMAT0019913) and homologs or orthologs in other species. The hsa-miR-4763-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4763-3p", "hsa-mir-4763" (miRBase Accession No. MI0017404, SEQ ID NO: 361) is known to have a hairpin-like structure.
[0269] As used herein, the term "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" includes the hsa-miR-3620-5p gene described in SEQ ID NO: 144 (miRBase Accession No. MIMAT0022967) and homologs or orthologs in other biological species. The hsa-miR-3620-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of "hsa-miR-3620-5p," "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 362) is known to have a hairpin-like structure.
[0270] As used herein, the term “hsa-miR-3195 gene” or “hsa-miR-3195” includes the hsa-miR-3195 gene described in SEQ ID NO: 145 (miRBase Accession No. MIMAT0015079) and homologs or orthologs in other species. The hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3195,” “hsa-mir-3195” (miRBase Accession No. MI0014240, SEQ ID NO: 363) is known to have a hairpin-like structure.
[0271] As used herein, the term "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" includes the hsa-miR-6842-5p gene described in SEQ ID NO: 146 (miRBase Accession No. MIMAT0027586) and homologs or orthologs in other species. The hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6842-5p", "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 364) is known to have a hairpin-like structure.
[0272] As used herein, the term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" includes the hsa-miR-4707-5p gene described in SEQ ID NO: 147 (miRBase Accession No. MIMAT0019807) and homologs or orthologs in other species. The hsa-miR-4707-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4707-5p", "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 365) is known to have a hairpin-like structure.
[0273] As used herein, the term "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" includes the hsa-miR-642a-3p gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0020924) and homologs or orthologs in other species. The hsa-miR-642a-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-642a-3p", "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 366) is known to have a hairpin-like structure.
[0274] As used herein, the term "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" includes the hsa-miR-7113-3p gene described in SEQ ID NO: 149 (miRBase Accession No. MIMAT0028124) and homologs or orthologs in other species. The hsa-miR-7113-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7113-3p", "hsa-mir-7113" (miRBase Accession No. MI0022964, SEQ ID NO: 367) is known to have a hairpin-like structure.
[0275] As used herein, the term "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" includes the hsa-miR-4728-5p gene described in SEQ ID NO: 150 (miRBase Accession No. MIMAT0019849) and homologs or orthologs in other species. The hsa-miR-4728-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4728-5p", "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 368) is known to have a hairpin-like structure.
[0276] As used herein, the term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" includes the hsa-miR-5195-3p gene described in SEQ ID NO: 151 (miRBase Accession No. MIMAT0021127) and homologs or orthologs in other species. The hsa-miR-5195-3p gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, Vol. 25, pp. 1389-1399. Furthermore, as a precursor of "hsa-miR-5195-3p," "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 369) is known to have a hairpin-like structure.
[0277] As used herein, the term "hsa-miR-1185-1-3p gene" or "hsa-miR-1185-1-3p" includes the hsa-miR-1185-1-3p gene described in SEQ ID NO: 152 (miRBase Accession No. MIMAT0022838) and homologs or orthologs in other biological species. The hsa-miR-1185-1-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-1185-1-3p", "hsa-mir-1185-1" (miRBase Accession No. MI0003844, SEQ ID NO: 370) is known to have a hairpin-like structure.
[0278] As used herein, the term "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" includes the hsa-miR-6774-5p gene described in SEQ ID NO: 153 (miRBase Accession No. MIMAT0027448) and homologs or orthologs in other species. The hsa-miR-6774-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6774-5p," "hsa-mir-6774" (miRBase Accession No. MI0022619, SEQ ID NO: 371) is known to have a hairpin-like structure.
[0279] As used herein, the term “hsa-miR-8059 gene” or “hsa-miR-8059” includes the hsa-miR-8059 gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0030986) and homologs or orthologs in other species. The hsa-miR-8059 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. In addition, as a precursor of “hsa-miR-8059”, “hsa-mir-8059” (miRBase Accession No. MI0025895, SEQ ID NO: 372) is known to have a hairpin-like structure.
[0280] As used herein, the term “hsa-miR-3131 gene” or “hsa-miR-3131” includes the hsa-miR-3131 gene described in SEQ ID NO: 155 (miRBase Accession No. MIMAT0014996) and homologs or orthologs in other species. The hsa-miR-3131 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3131,” “hsa-mir-3131” (miRBase Accession No. MI0014151, SEQ ID NO: 373) is known to have a hairpin-like structure.
[0281] As used herein, the term "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" includes the hsa-miR-7847-3p gene described in SEQ ID NO: 156 (miRBase Accession No. MIMAT0030422) and homologs or orthologs in other species. The hsa-miR-7847-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Furthermore, as a precursor of "hsa-miR-7847-3p", "hsa-mir-7847" (miRBase Accession No. MI0025517, SEQ ID NO: 374) is known to have a hairpin-like structure.
[0282] As used herein, the term "hsa-miR-4463 gene" or "hsa-miR-4463" includes the hsa-miR-4463 gene described in SEQ ID NO: 157 (miRBase Accession No. MIMAT0018987) and homologs or orthologs in other species. The hsa-miR-4463 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4463", "hsa-mir-4463" (miRBase Accession No. MI0016811, SEQ ID NO: 375) is known to have a hairpin-like structure.
[0283] As used herein, the term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" includes the hsa-miR-128-2-5p gene described in SEQ ID NO: 158 (miRBase Accession No. MIMAT0031095) and homologs or orthologs in other species. The hsa-miR-128-2-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-128-2-5p", "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 376) is known to have a hairpin-like structure.
[0284] As used herein, the term "hsa-miR-4508 gene" or "hsa-miR-4508" includes the hsa-miR-4508 gene described in SEQ ID NO: 159 (miRBase Accession No. MIMAT0019045) and homologs or orthologs in other species. The hsa-miR-4508 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4508," "hsa-mir-4508" (miRBase Accession No. MI0016872, SEQ ID NO: 377) is known to have a hairpin-like structure.
[0285] As used herein, the term "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" includes the hsa-miR-6806-5p gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0027512) and homologs or orthologs in other species. The hsa-miR-6806-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6806-5p," "hsa-mir-6806" (miRBase Accession No. MI0022651, SEQ ID NO: 378) is known to have a hairpin-like structure.
[0286] As used herein, the term "hsa-miR-7111-5p gene" or "hsa-miR-7111-5p" includes the hsa-miR-7111-5p gene described in SEQ ID NO: 161 (miRBase Accession No. MIMAT0028119) and homologs or orthologs in other species. The hsa-miR-7111-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-7111-5p", "hsa-mir-7111" (miRBase Accession No. MI0022962, SEQ ID NO: 379) is known to have a hairpin-like structure.
[0287] As used herein, the term “hsa-miR-6782-5p gene” or “hsa-miR-6782-5p” includes the hsa-miR-6782-5p gene described in SEQ ID NO: 162 (miRBase Accession No. MIMAT0027464) and homologs or orthologs in other species. The hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of “hsa-miR-6782-5p,” “hsa-mir-6782” (miRBase Accession No. MI0022627, SEQ ID NO: 380) is known to have a hairpin-like structure.
[0288] As used herein, the term "hsa-miR-4734 gene" or "hsa-miR-4734" includes the hsa-miR-4734 gene described in SEQ ID NO: 163 (miRBase Accession No. MIMAT0019859) and homologs or orthologs in other species. The hsa-miR-4734 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4734," "hsa-mir-4734" (miRBase Accession No. MI0017371, SEQ ID NO: 381) is known to have a hairpin-like structure.
[0289] As used herein, the term “hsa-miR-3162-5p gene” or “hsa-miR-3162-5p” includes the hsa-miR-3162-5p gene described in SEQ ID NO: 164 (miRBase Accession No. MIMAT0015036) and homologs or orthologs in other species. The hsa-miR-3162-5p gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3162-5p,” “hsa-mir-3162” (miRBase Accession No. MI0014192, SEQ ID NO: 382) is known to have a hairpin-like structure.
[0290] As used herein, the term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" includes the hsa-miR-887-3p gene described in SEQ ID NO: 165 (miRBase Accession No. MIMAT0004951) and homologs or orthologs in other species. The hsa-miR-887-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-887-3p", "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 383) is known to have a hairpin-like structure.
[0291] As used herein, the term "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" includes the hsa-miR-6752-5p gene described in SEQ ID NO: 166 (miRBase Accession No. MIMAT0027404) and homologs or orthologs in other species. The hsa-miR-6752-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6752-5p," "hsa-mir-6752" (miRBase Accession No. MI0022597, SEQ ID NO: 384) is known to have a hairpin-like structure.
[0292] As used herein, the term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" includes the hsa-miR-6724-5p gene described in SEQ ID NO: 167 (miRBase Accession No. MIMAT0025856) and homologs or orthologs in other species. The hsa-miR-6724-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6724-5p," "hsa-mir-6724" (miRBase Accession No. MI0022559, SEQ ID NO: 385) is known to have a hairpin-like structure.
[0293] As used herein, the term "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" includes the hsa-miR-23b-3p gene described in SEQ ID NO: 168 (miRBase Accession No. MIMAT0000418) and homologs or orthologs in other species. The hsa-miR-23b-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-23b-3p", "hsa-mir-23b" (miRBase Accession No. MI0000439, SEQ ID NO: 386) is known to have a hairpin-like structure.
[0294] As used herein, the term "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" includes the hsa-miR-23a-3p gene described in SEQ ID NO: 169 (miRBase Accession No. MIMAT0000078) and homologs or orthologs in other species. The hsa-miR-23a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. Furthermore, as a precursor of "hsa-miR-23a-3p", "hsa-mir-23a" (miRBase Accession No. MI0000079, SEQ ID NO: 387) is known to have a hairpin-like structure.
[0295] As used herein, the term "hsa-miR-625-3p gene" or "hsa-miR-625-3p" includes the hsa-miR-625-3p gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0004808) and homologs or orthologs in other species. The hsa-miR-625-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-625-3p", "hsa-mir-625" (miRBase Accession No. MI0003639, SEQ ID NO: 388) is known to have a hairpin-like structure.
[0296] As used herein, the term "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" includes the hsa-miR-1228-3p gene described in SEQ ID NO: 171 (miRBase Accession No. MIMAT0005583) and homologs or orthologs in other biological species. The hsa-miR-1228-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1228-3p", "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 316) is known to have a hairpin-like structure.
[0297] As used herein, the term "hsa-miR-614 gene" or "hsa-miR-614" includes the hsa-miR-614 gene described in SEQ ID NO: 172 (miRBase Accession No. MIMAT0003282) and homologs or orthologs in other species. The hsa-miR-614 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, as a precursor of "hsa-miR-614", "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 389) is known to have a hairpin-like structure.
[0298] As used herein, the term "hsa-miR-1913 gene" or "hsa-miR-1913" includes the hsa-miR-1913 gene described in SEQ ID NO: 173 (miRBase Accession No. MIMAT0007888) and homologs or orthologs in other biological species. The hsa-miR-1913 gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. In addition, as a precursor of "hsa-miR-1913", "hsa-mir-1913" (miRBase Accession No. MI0008334, SEQ ID NO: 390) is known to have a hairpin-like structure.
[0299] As used herein, the term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" includes the hsa-miR-92a-2-5p gene described in SEQ ID NO: 174 (miRBase Accession No. MIMAT0004508) and homologs or orthologs in other biological species. The hsa-miR-92a-2-5p gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. Furthermore, as a precursor of "hsa-miR-92a-2-5p", "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 391) is known to have a hairpin-like structure.
[0300] As used herein, the term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" includes the hsa-miR-187-5p gene described in SEQ ID NO: 175 (miRBase Accession No. MIMAT0004561) and homologs or orthologs in other species. The hsa-miR-187-5p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. Furthermore, as a precursor of "hsa-miR-187-5p", "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 392) is known to have a hairpin-like structure.
[0301] As used herein, the term “hsa-miR-16-5p gene” or “hsa-miR-16-5p” includes the hsa-miR-16-5p gene described in SEQ ID NO: 176 (miRBase Accession No. MIMAT0000069) and homologs or orthologs of other biological species. The hsa-miR-16-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. Furthermore, as precursors of “hsa-miR-16-5p,” “hsa-mir-16-1” and “hsa-mir-16-2” (miRBase Accession Nos. MI0000070 and MI0000115, SEQ ID NOs. 393 and 394) are known.
[0302] As used herein, the term "hsa-miR-92b-3p gene" or "hsa-miR-92b-3p" includes the hsa-miR-92b-3p gene described in SEQ ID NO: 177 (miRBase Accession No. MIMAT0003218) and homologs or orthologs in other species. The hsa-miR-92b-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-92b-3p", "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 395) is known to have a hairpin-like structure.
[0303] As used herein, the term "hsa-miR-150-3p gene" or "hsa-miR-150-3p" includes the hsa-miR-150-3p gene described in SEQ ID NO: 178 (miRBase Accession No. MIMAT0004610) and homologs or orthologs in other species. The hsa-miR-150-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-150-3p", "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 396) is known to have a hairpin-like structure.
[0304] As used herein, the term "hsa-miR-564 gene" or "hsa-miR-564" includes the hsa-miR-564 gene described in SEQ ID NO: 179 (miRBase Accession No. MIMAT0003228) and homologs or orthologs in other species. The hsa-miR-564 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, as a precursor of "hsa-miR-564", "hsa-mir-564" (miRBase Accession No. MI0003570, SEQ ID NO: 397) is known to have a hairpin-like structure.
[0305] As used herein, the term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" includes the hsa-miR-125a-3p gene described in SEQ ID NO: 180 (miRBase Accession No. MIMAT0004602) and homologs or orthologs in other species. The hsa-miR-125a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-125a-3p", "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 398) is known to have a hairpin-like structure.
[0306] As used herein, the term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" includes the hsa-miR-92b-5p gene described in SEQ ID NO: 181 (miRBase Accession No. MIMAT0004792) and homologs or orthologs in other species. The hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-92b-5p", "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 395) is known to have a hairpin-like structure.
[0307] As used herein, the term "hsa-miR-92a-3p gene" or "hsa-miR-92a-3p" includes the hsa-miR-92a-3p gene described in SEQ ID NO: 182 (miRBase Accession No. MIMAT0000092) and homologs or orthologs in other biological species. The hsa-miR-92a-3p gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. Furthermore, as precursors of "hsa-miR-92a-3p", "hsa-mir-92a-1" and "hsa-mir-92a-2" (miRBase Accession Nos. MI0000093 and MI0000094, SEQ ID NOs. 399 and 391) are known.
[0308] As used herein, the term "hsa-miR-663a gene" or "hsa-miR-663a" includes the hsa-miR-663a gene described in SEQ ID NO: 183 (miRBase Accession No. MIMAT0003326) and homologs or orthologs in other species. The hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-663a", "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 400) is known to have a hairpin-like structure.
[0309] As used herein, the term “hsa-miR-4688 gene” or “hsa-miR-4688” includes the hsa-miR-4688 gene described in SEQ ID NO: 184 (miRBase Accession No. MIMAT0019777) and homologs or orthologs in other species. The hsa-miR-4688 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4688,” “hsa-mir-4688” (miRBase Accession No. MI0017321, SEQ ID NO: 401) is known to have a hairpin-like structure.
[0310] As used herein, the term “hsa-miR-4648 gene” or “hsa-miR-4648” includes the hsa-miR-4648 gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0019710) and homologs or orthologs in other species. The hsa-miR-4648 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of “hsa-miR-4648,” “hsa-mir-4648” (miRBase Accession No. MI0017275, SEQ ID NO: 402) is known to have a hairpin-like structure.
[0311] As used herein, the term "hsa-miR-6085 gene" or "hsa-miR-6085" includes the hsa-miR-6085 gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0023710) and homologs or orthologs in other species. The hsa-miR-6085 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. Furthermore, as a precursor of "hsa-miR-6085," "hsa-mir-6085" (miRBase Accession No. MI0020362, SEQ ID NO: 403) is known to have a hairpin-like structure.
[0312] As used herein, the term “hsa-miR-6126 gene” or “hsa-miR-6126” includes the hsa-miR-6126 gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0024599) and homologs or orthologs in other species. The hsa-miR-6126 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of “hsa-miR-6126,” “hsa-mir-6126” (miRBase Accession No. MI0021260, SEQ ID NO: 404) is known to have a hairpin-like structure.
[0313] As used herein, the term "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" includes the hsa-miR-6880-5p gene described in SEQ ID NO: 188 (miRBase Accession No. MIMAT0027660) and homologs or orthologs in other species. The hsa-miR-6880-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6880-5p," "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 405) is known to have a hairpin-like structure.
[0314] As used herein, the term "hsa-miR-328-5p gene" or "hsa-miR-328-5p" includes the hsa-miR-328-5p gene described in SEQ ID NO: 189 (miRBase Accession No. MIMAT0026486) and homologs or orthologs in other species. The hsa-miR-328-5p gene can be obtained by the method described in Kim J et al., 2004, Proc Natl Acad Sci U SA, Vol. 101, pp. 360-365. Furthermore, as a precursor of "hsa-miR-328-5p", "hsa-mir-328" (miRBase Accession No. MI0000804, SEQ ID NO: 406) is known to have a hairpin-like structure.
[0315] As used herein, the term "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" includes the hsa-miR-6768-5p gene described in SEQ ID NO: 190 (miRBase Accession No. MIMAT0027436) and homologs or orthologs in other species. The hsa-miR-6768-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6768-5p", "hsa-mir-6768" (miRBase Accession No. MI0022613, SEQ ID NO: 407) is known to have a hairpin-like structure.
[0316] As used herein, the term “hsa-miR-3180 gene” or “hsa-miR-3180” includes the hsa-miR-3180 gene described in SEQ ID NO: 191 (miRBase Accession No. MIMAT0018178) and homologs or orthologs in other biological species. The hsa-miR-3180 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, as precursors of “hsa-miR-3180”, “hsa-mir-3180-4” and “hsa-mir-3180-5” (miRBase Accession Nos. MI0016408, MI0016409, SEQ ID NOs: 408, 409) are known as hairpin-like structures.
[0317] As used herein, the term "hsa-miR-6087 gene" or "hsa-miR-6087" includes the hsa-miR-6087 gene described in SEQ ID NO: 192 (miRBase Accession No. MIMAT0023712) and homologs or orthologs in other species. The hsa-miR-6087 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor of "hsa-miR-6087," "hsa-mir-6087" (miRBase Accession No. MI0020364, SEQ ID NO: 410) is known to form a hairpin-like structure.
[0318] As used herein, the term “hsa-miR-1273g-3p gene” or “hsa-miR-1273g-3p” includes the hsa-miR-1273g-3p gene described in SEQ ID NO: 193 (miRBase Accession No. MIMAT0022742) and homologs or orthologs in other biological species. The hsa-miR-1273g-3p gene can be obtained by the method described in Reshmi G et al., 2011, Genomics, Vol. 97, pp. 333-340. In addition, as a precursor of “hsa-miR-1273g-3p”, “hsa-mir-1273g” (miRBase Accession No. MI0018003, SEQ ID NO: 411) is known to have a hairpin-like structure.
[0319] As used herein, the term "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" includes the hsa-miR-1225-5p gene described in SEQ ID NO: 194 (miRBase Accession No. MIMAT0005572) and homologs or orthologs in other species. The hsa-miR-1225-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1225-5p", "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 303) is known to have a hairpin-like structure.
[0320] As used herein, the term “hsa-miR-3196 gene” or “hsa-miR-3196” includes the hsa-miR-3196 gene described in SEQ ID NO: 195 (miRBase Accession No. MIMAT0015080) and homologs or orthologs in other species. The hsa-miR-3196 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Furthermore, as a precursor of “hsa-miR-3196,” “hsa-mir-3196” (miRBase Accession No. MI0014241, SEQ ID NO: 412) is known to have a hairpin-like structure.
[0321] As used herein, the term "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" includes the hsa-miR-4695-5p gene described in SEQ ID NO: 196 (miRBase Accession No. MIMAT0019788) and homologs or orthologs in other species. The hsa-miR-4695-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4695-5p", "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 413) is known to have a hairpin-like structure.
[0322] As used herein, the term "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" includes the hsa-miR-6732-5p gene described in SEQ ID NO: 197 (miRBase Accession No. MIMAT0027365) and homologs or orthologs in other species. The hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6732-5p," "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 414) is known to have a hairpin-like structure.
[0323] As used herein, the term "hsa-miR-638 gene" or "hsa-miR-638" includes the hsa-miR-638 gene described in SEQ ID NO: 198 (miRBase Accession No. MIMAT0003308) and homologs or orthologs in other species. The hsa-miR-638 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor of "hsa-miR-638," "hsa-mir-638" (miRBase Accession No. MI0003653, SEQ ID NO: 415) is known to have a hairpin-like structure.
[0324] As used herein, the term "hsa-miR-6813-5p gene" or "hsa-miR-6813-5p" includes the hsa-miR-6813-5p gene described in SEQ ID NO: 199 (miRBase Accession No. MIMAT0027526) and homologs or orthologs in other species. The hsa-miR-6813-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6813-5p", "hsa-mir-6813" (miRBase Accession No. MI0022658, SEQ ID NO: 416) is known to have a hairpin-like structure.
[0325] As used herein, the term "hsa-miR-665 gene" or "hsa-miR-665" includes the hsa-miR-665 gene described in SEQ ID NO: 200 (miRBase Accession No. MIMAT0004952) and homologs or orthologs in other species. The hsa-miR-665 gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-665," "hsa-mir-665" (miRBase Accession No. MI0005563, SEQ ID NO: 417) is known to have a hairpin-like structure.
[0326] As used herein, the term “hsa-miR-486-3p gene” or “hsa-miR-486-3p” includes the hsa-miR-486-3p gene described in SEQ ID NO: 201 (miRBase Accession No. MIMAT0004762) and homologs or orthologs in other species. The hsa-miR-486-3p gene can be obtained by the method described in Fu H et al., 2005, FEBS Lett, Vol. 579, pp. 3849-3854. Furthermore, as precursors of “hsa-miR-486-3p,” “hsa-mir-486” and “hsa-mir-486-2” (miRBase Accession Nos. MI0002470, MI0023622, SEQ ID NOs. 418, 419) are known.
[0327] As used herein, the term "hsa-miR-4466 gene" or "hsa-miR-4466" includes the hsa-miR-4466 gene described in SEQ ID NO: 202 (miRBase Accession No. MIMAT0018993) and homologs or orthologs in other species. The hsa-miR-4466 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4466", "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 420) is known to have a hairpin-like structure.
[0328] As used herein, the term "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" includes the hsa-miR-30c-1-3p gene described in SEQ ID NO: 203 (miRBase Accession No. MIMAT0004674) and homologs or orthologs in other biological species. The hsa-miR-30c-1-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, pp. 735-739. Furthermore, as a precursor of "hsa-miR-30c-1-3p", "hsa-mir-30c-1" (miRBase Accession No. MI0000736, SEQ ID NO: 421) is known to have a hairpin-like structure.
[0329] As used herein, the term "hsa-miR-3621 gene" or "hsa-miR-3621" includes the hsa-miR-3621 gene described in SEQ ID NO: 204 (miRBase Accession No. MIMAT0018002) and homologs or orthologs in other species. The hsa-miR-3621 gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of "hsa-miR-3621," "hsa-mir-3621" (miRBase Accession No. MI0016012, SEQ ID NO: 422) is known to have a hairpin-like structure.
[0330] As used herein, the term "hsa-miR-6743-5p gene" or "hsa-miR-6743-5p" includes the hsa-miR-6743-5p gene described in SEQ ID NO: 205 (miRBase Accession No. MIMAT0027387) and homologs or orthologs in other species. The hsa-miR-6743-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6743-5p", "hsa-mir-6743" (miRBase Accession No. MI0022588, SEQ ID NO: 423) is known to have a hairpin-like structure.
[0331] As used herein, the term “hsa-miR-4298 gene” or “hsa-miR-4298” includes the hsa-miR-4298 gene described in SEQ ID NO: 206 (miRBase Accession No. MIMAT0016852) and homologs or orthologs in other species. The hsa-miR-4298 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. In addition, as a precursor of “hsa-miR-4298”, “hsa-mir-4298” (miRBase Accession No. MI0015830, SEQ ID NO: 424) is known to have a hairpin-like structure.
[0332] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" includes the hsa-miR-4741 gene described in SEQ ID NO: 207 (miRBase Accession No. MIMAT0019871) and homologs or orthologs in other species. The hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4741," "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 425) is known to have a hairpin-like structure.
[0333] As used herein, the term "hsa-miR-3619-3p gene" or "hsa-miR-3619-3p" includes the hsa-miR-3619-3p gene described in SEQ ID NO: 208 (miRBase Accession No. MIMAT0019219) and homologs or orthologs in other biological species. The hsa-miR-3619-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. Furthermore, as a precursor of "hsa-miR-3619-3p", "hsa-mir-3619" (miRBase Accession No. MI0016009, SEQ ID NO: 426) is known to have a hairpin-like structure.
[0334] As used herein, the term "hsa-miR-6824-5p gene" or "hsa-miR-6824-5p" includes the hsa-miR-6824-5p gene described in SEQ ID NO: 209 (miRBase Accession No. MIMAT0027548) and homologs or orthologs in other species. The hsa-miR-6824-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6824-5p," "hsa-mir-6824" (miRBase Accession No. MI0022669, SEQ ID NO: 427) is known to have a hairpin-like structure.
[0335] As used herein, the term “hsa-miR-5698 gene” or “hsa-miR-5698” includes the hsa-miR-5698 gene described in SEQ ID NO: 210 (miRBase Accession No. MIMAT0022491) and homologs or orthologs in other species. The hsa-miR-5698 gene can be obtained by the method described in Watahiki A et al., 2011, PLoS One, Vol. 6, e24950. In addition, as a precursor of “hsa-miR-5698”, “hsa-mir-5698” (miRBase Accession No. MI0019305, SEQ ID NO: 428) is known to have a hairpin-like structure.
[0336] As used herein, the term "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" includes the hsa-miR-371a-5p gene described in SEQ ID NO: 211 (miRBase Accession No. MIMAT0004687) and homologs or orthologs in other species. The hsa-miR-371a-5p gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, Vol. 270, pp. 488-498. Furthermore, as a precursor of "hsa-miR-371a-5p", "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 429) is known to have a hairpin-like structure.
[0337] As used herein, the term "hsa-miR-4488 gene" or "hsa-miR-4488" includes the hsa-miR-4488 gene described in SEQ ID NO: 212 (miRBase Accession No. MIMAT0019022) and homologs or orthologs in other species. The hsa-miR-4488 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4488", "hsa-mir-4488" (miRBase Accession No. MI0016849, SEQ ID NO: 430) is known to have a hairpin-like structure.
[0338] As used herein, the term "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" includes the hsa-miR-1233-5p gene described in SEQ ID NO: 213 (miRBase Accession No. MIMAT0022943) and homologs or orthologs in other biological species. The hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as precursors of "hsa-miR-1233-5p", "hsa-mir-1233-1" and "hsa-mir-1233-2" (miRBase Accession Nos. MI0006323 and MI0015973, SEQ ID NOs. 431 and 432) are known as hairpin-like structure precursors.
[0339] As used herein, the term "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" includes the hsa-miR-4723-5p gene described in SEQ ID NO: 214 (miRBase Accession No. MIMAT0019838) and homologs or orthologs in other species. The hsa-miR-4723-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4723-5p", "hsa-mir-4723" (miRBase Accession No. MI0017359, SEQ ID NO: 433) is known to have a hairpin-like structure.
[0340] As used herein, the term “hsa-miR-24-3p gene” or “hsa-miR-24-3p” includes the hsa-miR-24-3p gene described in SEQ ID NO: 215 (miRBase Accession No. MIMAT0000080) and homologs or orthologs in other biological species. The hsa-miR-24-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, pp. 853-858. In addition, as precursors of “hsa-miR-24-3p”, “hsa-mir-24-1” and “hsa-mir-24-2” (miRBase Accession Nos. MI0000080, MI0000081, SEQ ID NOs: 434, 435) are known as hairpin-like structure precursors.
[0341] As used herein, the term "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" includes the hsa-miR-1238-5p gene described in SEQ ID NO: 216 (miRBase Accession No. MIMAT0022947) and homologs or orthologs in other species. The hsa-miR-1238-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor of "hsa-miR-1238-5p", "hsa-mir-1238" (miRBase Accession No. MI0006328, SEQ ID NO: 436) is known to have a hairpin-like structure.
[0342] As used herein, the term "hsa-miR-4442 gene" or "hsa-miR-4442" includes the hsa-miR-4442 gene described in SEQ ID NO: 217 (miRBase Accession No. MIMAT0018960) and homologs or orthologs in other species. The hsa-miR-4442 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4442", "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 437) is known to have a hairpin-like structure.
[0343] As used herein, the term "hsa-miR-3928-3p gene" or "hsa-miR-3928-3p" includes the hsa-miR-3928-3p gene described in SEQ ID NO: 218 (miRBase Accession No. MIMAT0018205) and homologs or orthologs in other species. The hsa-miR-3928-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. Furthermore, as a precursor of "hsa-miR-3928-3p", "hsa-mir-3928" (miRBase Accession No. MI0016438, SEQ ID NO: 438) is known to have a hairpin-like structure.
[0344] As used herein, the term "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" includes the hsa-miR-6716-5p gene described in SEQ ID NO: 219 (miRBase Accession No. MIMAT0025844) and homologs or orthologs in other species. The hsa-miR-6716-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Furthermore, as a precursor of "hsa-miR-6716-5p," "hsa-mir-6716" (miRBase Accession No. MI0022550, SEQ ID NO: 439) is known to have a hairpin-like structure.
[0345] As used herein, the term “hsa-miR-6089 gene” or “hsa-miR-6089” includes the hsa-miR-6089 gene described in SEQ ID NO: 220 (miRBase Accession No. MIMAT0023714) and homologs or orthologs in other biological species. The hsa-miR-6089 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. In addition, as precursors of “hsa-miR-6089”, “hsa-mir-6089-1” and “hsa-mir-6089-2” (miRBase Accession Nos. MI0020366, MI0023563, SEQ ID NOs: 440, 441) are known as hairpin-like structure-forming precursors.
[0346] As used herein, the term “hsa-miR-6124 gene” or “hsa-miR-6124” includes the hsa-miR-6124 gene described in SEQ ID NO: 221 (miRBase Accession No. MIMAT0024597) and homologs or orthologs in other species. The hsa-miR-6124 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, Vol. 86, pp. 5278-5287. Furthermore, as a precursor of “hsa-miR-6124,” “hsa-mir-6124” (miRBase Accession No. MI0021258, SEQ ID NO: 442) is known to have a hairpin-like structure.
[0347] As used herein, the term "hsa-miR-6778-5p gene" or "hsa-miR-6778-5p" includes the hsa-miR-6778-5p gene described in SEQ ID NO: 222 (miRBase Accession No. MIMAT0027456) and homologs or orthologs in other species. The hsa-miR-6778-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6778-5p", "hsa-mir-6778" (miRBase Accession No. MI0022623, SEQ ID NO: 443) is known to have a hairpin-like structure.
[0348] As used herein, the term "hsa-miR-557 gene" or "hsa-miR-557" includes the hsa-miR-557 gene described in SEQ ID NO: 223 (miRBase Accession No. MIMAT0003221) and homologs or orthologs in other species. The hsa-miR-557 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci USA, Vol. 103, pp. 3687-3692. In addition, as a precursor of "hsa-miR-557", "hsa-mir-557" (miRBase Accession No. MI0003563, SEQ ID NO: 444) is known to have a hairpin-like structure.
[0349] As used herein, the term "hsa-miR-6090 gene" or "hsa-miR-6090" includes the hsa-miR-6090 gene described in SEQ ID NO: 224 (miRBase Accession No. MIMAT0023715) and homologs or orthologs in other species. The hsa-miR-6090 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor of "hsa-miR-6090," "hsa-mir-6090" (miRBase Accession No. MI0020367, SEQ ID NO: 445) is known to have a hairpin-like structure.
[0350] As used herein, the term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" includes the hsa-miR-6757-5p gene described in SEQ ID NO: 714 (miRBase Accession No. MIMAT0027414) and homologs or orthologs in other species. The hsa-miR-6757-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6757-5p," "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 730) is known to have a hairpin-like structure.
[0351] As used herein, the term "hsa-miR-4448 gene" or "hsa-miR-4448" includes the hsa-miR-4448 gene described in SEQ ID NO: 715 (miRBase Accession No. MIMAT0018967) and homologs or orthologs in other species. The hsa-miR-4448 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4448", "hsa-mir-4448" (miRBase Accession No. MI0016791, SEQ ID NO: 731) is known to have a hairpin-like structure.
[0352] As used herein, the term "hsa-miR-671-5p gene" or "hsa-miR-671-5p" includes the hsa-miR-671-5p gene described in SEQ ID NO: 716 (miRBase Accession No. MIMAT0003880) and homologs or orthologs in other species. The hsa-miR-671-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, Vol. 16, pp. 1289-1298. Furthermore, as a precursor of "hsa-miR-671-5p", "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 732) is known to have a hairpin-like structure.
[0353] As used herein, the term “hsa-miR-3178 gene” or “hsa-miR-3178” includes the hsa-miR-3178 gene described in SEQ ID NO: 717 (miRBase Accession No. MIMAT0015055) and homologs or orthologs in other species. The hsa-miR-3178 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, as a precursor of “hsa-miR-3178”, “hsa-mir-3178” (miRBase Accession No. MI0014212, SEQ ID NO: 733) is known to have a hairpin-like structure.
[0354] As used herein, the term "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" includes the hsa-miR-4725-3p gene described in SEQ ID NO: 718 (miRBase Accession No. MIMAT0019844) and homologs or orthologs in other species. The hsa-miR-4725-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4725-3p", "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 734) is known to have a hairpin-like structure.
[0355] As used herein, the term "hsa-miR-940 gene" or "hsa-miR-940" includes the hsa-miR-940 gene described in SEQ ID NO: 719 (miRBase Accession No. MIMAT0004983) and homologs or orthologs in other species. The hsa-miR-940 gene can be obtained by the method described in Lui WO et al., 2007, A Cancer Res., Vol. 67, pp. 6031-6043. Furthermore, as a precursor of "hsa-miR-940", "hsa-mir-940" (miRBase Accession No. MI0005762, SEQ ID NO: 735) is known to have a hairpin-like structure.
[0356] As used herein, the term “hsa-miR-6789-5p gene” or “hsa-miR-6789-5p” includes the hsa-miR-6789-5p gene described in SEQ ID NO: 720 (miRBase Accession No. MIMAT0027478) and homologs or orthologs in other biological species. The hsa-miR-6789-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., 22, pp. 1634-1645. In addition, as a precursor of “hsa-miR-6789-5p”, “hsa-mir-6789” (miRBase Accession No. MI0022634, SEQ ID NO: 736) is known to have a hairpin-like structure.
[0357] As used herein, the term "hsa-miR-4484 gene" or "hsa-miR-4484" includes the hsa-miR-4484 gene described in SEQ ID NO: 721 (miRBase Accession No. MIMAT0019018) and homologs or orthologs in other species. The hsa-miR-4484 gene can be obtained by the method described in Jima DD et al., 2010, Blood., Vol. 116, e118-e127. Furthermore, as a precursor of "hsa-miR-4484", "hsa-mir-4484" (miRBase Accession No. MI0016845, SEQ ID NO: 737) is known to have a hairpin-like structure.
[0358] As used herein, the term "hsa-miR-4634 gene" or "hsa-miR-4634" includes the hsa-miR-4634 gene described in SEQ ID NO: 722 (miRBase Accession No. MIMAT0019691) and homologs or orthologs in other species. The hsa-miR-4634 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4634," "hsa-mir-4634" (miRBase Accession No. MI0017261, SEQ ID NO: 738) is known to have a hairpin-like structure.
[0359] As used herein, the term "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" includes the hsa-miR-4745-5p gene described in SEQ ID NO: 723 (miRBase Accession No. MIMAT0019878) and homologs or orthologs in other species. The hsa-miR-4745-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4745-5p", "hsa-mir-4745" (miRBase Accession No. MI0017384, SEQ ID NO: 739) is known to have a hairpin-like structure.
[0360] As used herein, the term "hsa-miR-4730 gene" or "hsa-miR-4730" includes the hsa-miR-4730 gene described in SEQ ID NO: 724 (miRBase Accession No. MIMAT0019852) and homologs or orthologs in other species. The hsa-miR-4730 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4730", "hsa-mir-4730" (miRBase Accession No. MI0017367, SEQ ID NO: 740) is known to have a hairpin-like structure.
[0361] As used herein, the term "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" includes the hsa-miR-6803-5p gene described in SEQ ID NO: 725 (miRBase Accession No. MIMAT0027506) and homologs or orthologs in other species. The hsa-miR-6803-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6803-5p", "hsa-mir-6803" (miRBase Accession No. MI0022648, SEQ ID NO: 741) is known to have a hairpin-like structure.
[0362] As used herein, the term "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" includes the hsa-miR-6798-5p gene described in SEQ ID NO: 726 (miRBase Accession No. MIMAT0027496) and homologs or orthologs in other species. The hsa-miR-6798-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Furthermore, as a precursor of "hsa-miR-6798-5p", "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 742) is known to have a hairpin-like structure.
[0363] As used herein, the term “hsa-miR-3648 gene” or “hsa-miR-3648” includes the hsa-miR-3648 gene described in SEQ ID NO: 727 (miRBase Accession No. MIMAT0018068) and homologs or orthologs in other species. The hsa-miR-3648 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, Vol. 38, pp. 6234-6246. Furthermore, as a precursor of “hsa-miR-3648,” “hsa-mir-3648” (miRBase Accession No. MI0016048, SEQ ID NO: 743) is known to have a hairpin-like structure.
[0364] As used herein, the term "hsa-miR-4783-3p gene" or "hsa-miR-4783-3p" includes the hsa-miR-4783-3p gene described in SEQ ID NO: 728 (miRBase Accession No. MIMAT0019947) and homologs or orthologs in other species. The hsa-miR-4783-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor of "hsa-miR-4783-3p", "hsa-mir-4783" (miRBase Accession No. MI0017428, SEQ ID NO: 744) is known to have a hairpin-like structure.
[0365] As used herein, the term “hsa-miR-6836-3p gene” or “hsa-miR-6836-3p” includes the hsa-miR-6836-3p gene described in SEQ ID NO: 729 (miRBase Accession No. MIMAT0027575) and homologs or orthologs in other biological species. The hsa-miR-6836-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., 22, pp. 1634-1645. In addition, as a precursor of “hsa-miR-6836-3p”, “hsa-mir-6836” (miRBase Accession No. MI0022682, SEQ ID NO: 745) is known to have a hairpin-like structure.
[0366] In addition, when a mature miRNA is cut out from an RNA precursor that forms a hairpin-like structure as a mature miRNA, sometimes one to several bases before and after the sequence are cut out short or long, and base substitution occurs to become a mutant, which is called isomiR (Morin RD. et al., 2008, Genome Res., Vol. 18, p. 610-621). In miRBase version 20, in addition to the base sequences shown in any one of sequence numbers 1 to 224 and 714 to 729, a plurality of mutants and fragments of the base sequences shown in any one of sequence numbers 446 to 713 and 746 to 765, which are called isomiR, are also shown. These mutants can also be obtained as miRNAs having the base sequences shown in any one of sequence numbers 1 to 224 and 714 to 729.
[0367] That is, the sequence numbers 1, 3, 4, 6, 7, 10, 11, 13, 14, 16, 17, 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 a polynucleotide consisting of a base sequence in which u is t in the base sequence, as the longest variant registered in, for example, miRBase version 20,Serial numbers 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. ,
[0368] In addition, in the case of the serial numbers 1, 3, 4, 6, 7, 10, 11, 13, 14, 16, 17, 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 a polynucleotide consisting of a base sequence in which u is t in the base sequence, as, for example, the shortest variant registered in miRBase version 20,Serial numbers 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, 489, 491, 493, 495, 497, 499, 501, 503, 505, 507, 509, 511, 513, 515, 517, 519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545, 547, 549, 551, 553, 555, 557, 559, 561, 563, 565, 567, 569, 571, 573, 575, 577, 579, 581, 583, 585, 587, 589, 5 91, 593, 595, 597, 599, 601, 603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 629, 631, 633, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657, 659, 661, 663, 6 65, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685, 687, 689, 691, 693, 695, 697, 699, 701, 703, 705, 707, 709, 711, 713, 747, 749, 751, 753, 755, 757, 759, 761, 763 and 765.
[0369] In addition to these mutants and fragments, polynucleotides representing multiple isomiRs registered in miRBase, such as SEQ ID NOs: 1 to 224 and 714 to 729, can also be cited. Furthermore, examples of polynucleotides comprising the base sequences represented by any of SEQ ID NOs: 1 to 224 and 714 to 729 include the polynucleotides represented by any of SEQ ID NOs: 225 to 445 and 730 to 745, respectively, as precursors.
[0370] Table 1 lists the names and miRBase accession numbers of the genes represented by SEQ ID NOs: 1 to 765.
[0371] In this specification, "capable of specifically binding" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and is substantially unable to bind to other nucleic acids.
[0372] [Table 1]
[0373]
[0374]
[0375]
[0376]
[0377]
[0378]
[0379]
[0380]
[0381]
[0382]
[0383]
[0384]
[0385]
[0386]
[0387]
[0388]
[0389]
[0390]
[0391]
[0392]
[0393]
[0394]
[0395] This specification includes the contents described in the specification and drawings of Japanese Patent Application No. 2014-124880, which is the basis of the priority of this application.
[0396] Effects of the Invention
[0397] The present invention makes it possible to easily and accurately detect liver cancer. For example, using the measured values of several miRNAs in a patient's blood, serum, or plasma, which can be collected minimally invasively, as indicators, it is possible to easily detect whether a patient has liver cancer. BRIEF DESCRIPTION OF THE DRAWINGS
[0398] Figure 1 The figure shows the relationship between the base sequences of hsa-miR-1343-5p shown in sequence number 131 generated from hsa-mir-1343 shown in sequence number 225 as a precursor, and hsa-miR-1343-3p shown in sequence number 1.
[0399] Figure 2 Middle left figure: A graph showing the measured values of hsa-miR-1343-3p (SEQ ID NO. 1) in healthy subjects (100 people) and liver cancer patients (34 people) selected as the learning sample group as the vertical axis. The horizontal line in the figure represents the threshold value (7.09) for distinguishing the two groups, optimized by Fisher's discriminant analysis. Right figure: A graph showing the measured values of hsa-miR-1343-3p (SEQ ID NO. 1) in healthy subjects (50 people) and liver cancer patients (16 people) selected as the test sample group as the vertical axis. The horizontal line in the figure represents the threshold value (7.09) for distinguishing the two groups, set by the learning sample group.
[0400] Figure 3 Middle left figure: A graph showing the measured values of hsa-miR-1343-3p (sequence number 1) of healthy subjects (100 people, circles) and liver cancer patients (34 people, triangles) selected as the learning sample group as the horizontal axis and the measured values of hsa-miR-6726-5p (sequence number 2) as the vertical axis. The line in the figure represents the discriminant function (0 = 0.77x + y - 15.07) that discriminates the two groups, which was optimized by Fisher's discriminant analysis. Right figure: A graph showing the measured values of hsa-miR-1343-3p (sequence number 1) of healthy subjects (50 people, circles) and liver cancer patients (16 people, triangles) selected as the test sample group as the horizontal axis and the measured values of hsa-miR-6726-5p (sequence number 2) as the vertical axis. The line in the figure represents the threshold value (0=0.77x+y-15.07) for distinguishing the two groups, which was set based on the learning sample group.
[0401] Figure 4Upper middle figure: hsa-miR-6131 (SEQ ID NO. 7), hsa-miR-642a-3p (SEQ ID NO. 148), hsa-miR-7641 (SEQ ID NO. 9), hsa- The measured values of miR-6729-5p (SEQ ID NO: 27) were analyzed using Fisher's discriminant analysis to create a discriminant equation (0.88xhsa-miR-6131-1.58xhsa-miR-642a-3p+0.39xhsa-miR-7641-0.33xhsa-miR-6729-5p+5.19). This graph shows the discriminant score obtained using this discriminant equation on the vertical axis and the sample group on the horizontal axis. The dotted line in the figure indicates the discriminant boundary between the two groups, where the discriminant score is 0. 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 17 patients with liver cancer, 51 healthy subjects, 28 patients with pancreatic cancer, 37 patients with biliary cancer, 15 patients with colorectal cancer, 12 patients with gastric cancer, 25 patients with esophageal cancer, and 5 patients with benign pancreatic and biliary diseases, respectively, selected as the test specimen group. The discriminant score obtained by the discriminant formula generated by the learning specimen group is shown on the vertical axis, and the specimen group is shown on the horizontal axis. The dotted line in the figure represents the discrimination boundary between the two groups with a discrimination score of 0. DETAILED DESCRIPTION
[0402] The present invention will be described in further detail below.
[0403] 1. Target nucleic acid for liver cancer
[0404] Among the main target nucleic acids used as liver cancer markers for detecting the presence and / or absence of liver cancer or liver cancer cells using the above-defined liver cancer detection nucleic acid probes or primers of the present invention, hsa-miR-1343-3p, 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, hsa-miR-1249, hsa-miR-3679-3p, hsa-miR-6787-5p, hsa-miR- iR-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-miR-6816-5p, hsa-miR-4281, hsa-miR-6729-5p, hsa-miR-8069, hsa-miR-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, hsa-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-4665-5p, hsa-miR-7845-5p, hsa- miR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765-5p, hsa-miR-296-5p, hsa-miR-3675-3p, hsa-miR-6781-5p, hsa-miR-423-5p, hsa-miR-3663-3p, hs a-miR-6784-5p, hsa-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-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-6088, hsa-miR-6800-5p, hsa-miR-1246, hsa-miR-4467, hsa-miR-4419b, hsa-miR-1914-3p, hsa-miR-4 632-5p、hsa-miR-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、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-6808-5p、hsa-miR-44 49, hsa-miR-1199-5p, hsa-miR-1275, hsa-miR-4792, hsa-miR-4443, hsa-miR-6891-5p, hsa-miR-6826-5p, hsa-miR-6807-5p, hsa-miR-7150, hsa-mi R-4534, hsa-miR-4476, hsa-miR-4649-5p, hsa-miR-4525, hsa-miR-1915-3p, hsa-miR-4516, hsa-miR-4417, hsa-miR-642b-3p, hsa-miR-3141, hsa-m iR-5100, hsa-miR-6848-5p, hsa-miR-4739, hsa-miR-4459, hsa-miR-1237-5p, hsa-miR-296-3p, hsa-miR-4665-3p, hsa-miR-6786-5p, hsa-miR-4258At least one or more miRNAs among 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-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-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, 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-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-4783-3p, and hsa-miR-6836-3p. Further, other liver cancer markers that can be combined with these miRNAs, namely, selected from hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-625-3p, hsa-miR-1228-3p, hsa-miR-614, hsa-miR-1913, hsa-miR-92a-2-5p, hsa-miR-187-5p, hsa-miR-16-5p, hsa-miR-92b-3p,At least one of hsa-miR-150-3p, hsa-miR-564, hsa-miR-125a-3p, hsa-miR-92b-5p, hsa-miR-92a-3p, and hsa-miR-663a can also be preferably used as a target nucleic acid. Furthermore, other liver cancer markers that can be combined with these miRNAs 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- 1273g-3p, hsa-miR-1225-5p, hsa-miR-3196, hsa-miR-4695-5p, hsa-miR-6732-5p, hsa-miR-63 8. hsa-miR-6813-5p, hsa-miR-665, hsa-miR-486-3p, hsa-miR-4466, hsa-miR-30c-1-3p, hsa-mi R-3621, hsa-miR-6743-5p, hsa-miR-4298, 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-4723-5p, hsa-mi At least one miRNA selected from 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-557, and hsa-miR-6090 can also be preferably used as the target nucleic acid.
[0405] Among the above-mentioned miRNAs, for example, human genes containing the base sequences shown in any one of SEQ ID NOs: 1 to 224 and 714 to 729 (that is, hsa-miR-1343-3p, 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, 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-miR-6816-5p, hsa-miR-4281, hsa-miR-6729-5p, hsa-miR-8069, hsa-miR-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, hsa-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-4665-5p, hsa-miR-7845-5p, hsa-miR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765-5p, hsa-miR-296-5p, hsa-miR-3675-3p, 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-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-1229-5p、hsa-miR-6820-5p、hsa-miR-6777-5p、hsa-miR-3917、hsa-miR-5787、hsa-miR-4286、hsa-miR-687 7-5p、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、h sa-miR-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、h sa-miR-4638-5p, hsa-miR-6799-5p, hsa-miR-6861-5p, hsa-miR-6727-5p, hsa-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-6891-5p, hsa-miR-6826-5p, hsa-miR-6807-5p, hsa-miR-7150, hsa-miR-45 34, hsa-miR-4476, hsa-miR-4649-5p, hsa-miR-4525, hsa-miR-1915-3p, hsa-miR-4516, hsa-miR-4417, hsa-miR-642b-3p, hsa-miR-3141, hsa-miR -5100、hsa-miR-6848-5p、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-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-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-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, 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-6789-5p, hsa-miR-4484, hsa-miR-4634, hsa-miR-4745-5p, hsa-miR-4730, hsa-miR-6803-5p sa-miR-6798-5p、hsa-miR-3648、hsa-miR-4783-3p、hsa-miR-6836-3p、hsa-miR-23b-3p、hsa-miR-23a-3p、hsa-miR-625-3p、hsa-miR-1228-3p、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-miR-125a-3phsa-miR-92b-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-6 087, hsa-miR-1273g-3p, hsa-miR-1225-5p, hsa-miR-3196, 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-4298, 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-4723-5p, 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-557 and hsa-miR-6090), their homologs, their transcription products, and their mutants or derivatives. Here, genes, homologs, transcription products, mutants and derivatives are as defined above.
[0406] A preferred target nucleic acid is a human gene comprising the base sequence shown in any one of SEQ ID NOs: 1 to 765, or a transcription product thereof, more preferably the transcription product, ie, miRNA, or its precursor RNA, pri-miRNA or pre-miRNA.
[0407] The first target gene is the hsa-miR-1343-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0408] The second target gene is the hsa-miR-6726-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0409] The third target gene is the hsa-miR-6515-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0410] The fourth target gene is the hsa-miR-4651 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0411] The fifth target gene is the hsa-miR-4257 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0412] The sixth target gene is the hsa-miR-3188 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0413] The seventh target gene is the hsa-miR-6131 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0414] The eighth target gene is the hsa-miR-6766-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0415] The ninth target gene is the hsa-miR-7641 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0416] The tenth target gene is the hsa-miR-1249 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0417] The eleventh target gene is the hsa-miR-3679-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0418] The twelfth target gene is the hsa-miR-6787-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0419] The 13th target gene is the hsa-miR-4454 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0420] The 14th target gene is the hsa-miR-3135b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0421] The fifteenth target gene is the hsa-miR-6765-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0422] The 16th target gene is the hsa-miR-7975 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0423] The 17th target gene is the hsa-miR-204-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0424] The 18th target gene is the hsa-miR-7977 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0425] The 19th target gene is the hsa-miR-7110-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0426] The 20th target gene is the hsa-miR-6717-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0427] The 21st target gene is the hsa-miR-6870-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0428] The 22nd target gene is the hsa-miR-663b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0429] The 23rd target gene is the hsa-miR-6875-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0430] The 24th target gene is the hsa-miR-8072 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0431] The 25th target gene is the hsa-miR-6816-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0432] The 26th target gene is the hsa-miR-4281 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0433] The 27th target gene is the hsa-miR-6729-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0434] The 28th target gene is the hsa-miR-8069 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0435] The 29th target gene is the hsa-miR-4706 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0436] The 30th target gene is the hsa-miR-7108-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0437] The 31st target gene is the hsa-miR-4433b-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0438] The 32nd target gene is the hsa-miR-6893-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0439] The 33rd target gene is the hsa-miR-6857-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0440] The 34th target gene is the hsa-miR-1227-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0441] The 35th target gene is the hsa-miR-6741-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0442] The 36th target gene is the hsa-miR-451a gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0443] The 37th target gene is the hsa-miR-8063 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0444] The 38th target gene is the hsa-miR-3622a-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0445] The 39th target gene is the hsa-miR-615-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0446] The 40th target gene is the hsa-miR-128-1-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0447] The 41st target gene is the hsa-miR-6825-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0448] The 42nd target gene is the hsa-miR-1260b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0449] The 43rd target gene is the hsa-miR-4433-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0450] The 44th target gene is the hsa-miR-4665-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0451] The 45th target gene is the hsa-miR-7845-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0452] The 46th target gene is the hsa-miR-1908-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0453] The 47th target gene is the hsa-miR-6840-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0454] The 48th target gene is the hsa-miR-6765-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0455] The 49th target gene is the hsa-miR-296-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0456] The 50th target gene is the hsa-miR-3675-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0457] The 51st target gene is the hsa-miR-6781-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0458] The 52nd target gene is the hsa-miR-423-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0459] The 53rd target gene is the hsa-miR-3663-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0460] The 54th target gene is the hsa-miR-6784-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0461] The 55th target gene is the hsa-miR-6749-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0462] The 56th target gene is the hsa-miR-1231 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0463] The 57th target gene is the hsa-miR-4746-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0464] The 58th target gene is the hsa-miR-6780b-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0465] The 59th target gene is the hsa-miR-4758-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0466] The 60th target gene is the hsa-miR-3679-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0467] The 61st target gene is the hsa-miR-3184-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0468] The 62nd target gene is the hsa-miR-6125 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0469] The 63rd target gene is the hsa-miR-6721-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0470] The 64th target gene is the hsa-miR-6791-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0471] The 65th target gene is the hsa-miR-3185 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0472] The 66th target gene is the hsa-miR-1260a gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0473] The 67th target gene is the hsa-miR-3197 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0474] The 68th target gene is the hsa-miR-6845-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0475] The 69th target gene is the hsa-miR-6887-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0476] The 70th target gene is the hsa-miR-6738-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0477] The 71st target gene is the hsa-miR-6872-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0478] The 72nd target gene is the hsa-miR-4497 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0479] The 73rd target gene is the hsa-miR-1229-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0480] The 74th target gene is the hsa-miR-6820-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0481] The 75th target gene is the hsa-miR-6777-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0482] The 76th target gene is the hsa-miR-3917 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0483] The 77th target gene is the hsa-miR-5787 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0484] The 78th target gene is the hsa-miR-4286 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0485] The 79th target gene is the hsa-miR-6877-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0486] The 80th target gene is the hsa-miR-1225-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0487] The 81st target gene is the hsa-miR-6088 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0488] The 82nd target gene is the hsa-miR-6800-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0489] The 83rd target gene is the hsa-miR-1246 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0490] The 84th target gene is the hsa-miR-4467 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0491] The 85th target gene is the hsa-miR-4419b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0492] The 86th target gene is the hsa-miR-1914-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0493] The 87th target gene is the hsa-miR-4632-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0494] The 88th target gene is the hsa-miR-1915-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0495] The 89th target gene is the hsa-miR-3940-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0496] The 90th target gene is the hsa-miR-1185-2-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0497] The 91st target gene is the hsa-miR-6746-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0498] The 92nd target gene is the hsa-miR-5001-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0499] The 93rd target gene is the hsa-miR-1228-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0500] The 94th target gene is the hsa-miR-5572 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0501] The 95th target gene is the hsa-miR-4327 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0502] The 96th target gene is the hsa-miR-4638-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0503] The 97th target gene is the hsa-miR-6799-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0504] The 98th target gene is the hsa-miR-6861-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0505] The 99th target gene is the hsa-miR-6727-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0506] The 100th target gene is the hsa-miR-4513 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0507] The 101st target gene is the hsa-miR-6805-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0508] The 102nd target gene is the hsa-miR-6808-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0509] The 103rd target gene is the hsa-miR-4449 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0510] The 104th target gene is the hsa-miR-1199-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0511] The 105th target gene is the hsa-miR-1275 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0512] The 106th target gene is the hsa-miR-4792 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0513] The 107th target gene is the hsa-miR-4443 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0514] The 108th target gene is the hsa-miR-6891-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0515] The 109th target gene is the hsa-miR-6826-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0516] The 110th target gene is the hsa-miR-6807-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0517] The 111th target gene is the hsa-miR-7150 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0518] The 112th target gene is the hsa-miR-4534 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0519] The 113th target gene is the hsa-miR-4476 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0520] The 114th target gene is the hsa-miR-4649-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0521] The 115th target gene is the hsa-miR-4525 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0522] The 116th target gene is the hsa-miR-1915-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0523] The 117th target gene is the hsa-miR-4516 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0524] The 118th target gene is the hsa-miR-4417 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0525] The 119th target gene is the hsa-miR-642b-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0526] The 120th target gene is the hsa-miR-3141 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0527] The 121st target gene is the hsa-miR-5100 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0528] The 122nd target gene is the hsa-miR-6848-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0529] The 123rd target gene is the hsa-miR-4739 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0530] The 124th target gene is the hsa-miR-4459 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0531] The 125th target gene is the hsa-miR-1237-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0532] The 126th target gene is the hsa-miR-296-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0533] The 127th target gene is the hsa-miR-4665-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0534] The 128th target gene is the hsa-miR-6786-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0535] The 129th target gene is the hsa-miR-4258 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0536] The 130th target gene is the hsa-miR-6510-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0537] The 131st target gene is the hsa-miR-1343-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0538] The 132nd target gene is the hsa-miR-1247-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0539] The 133rd target gene is the hsa-miR-6805-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0540] The 134th target gene is the hsa-miR-4492 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0541] The 135th target gene is the hsa-miR-1469 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0542] The 136th target gene is the hsa-miR-1268b gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0543] The 137th target gene is the hsa-miR-6858-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0544] The 138th target gene is the hsa-miR-3937 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0545] The 139th target gene is the hsa-miR-939-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0546] The 140th target gene is the hsa-miR-3656 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0547] The 141st target gene is the hsa-miR-744-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0548] The 142nd target gene is the hsa-miR-4687-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0549] The 143rd target gene is the hsa-miR-4763-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0550] The 144th target gene is the hsa-miR-3620-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0551] The 145th target gene is the hsa-miR-3195 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0552] The 146th target gene is the hsa-miR-6842-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0553] The 147th target gene is the hsa-miR-4707-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0554] The 148th target gene is the hsa-miR-642a-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0555] The 149th target gene is the hsa-miR-7113-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0556] The 150th target gene is the hsa-miR-4728-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0557] The 151st target gene is the hsa-miR-5195-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0558] The 152nd target gene is the hsa-miR-1185-1-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0559] The 153rd target gene is the hsa-miR-6774-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0560] The 154th target gene is the hsa-miR-8059 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0561] The 155th target gene is the hsa-miR-3131 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0562] The 156th target gene is the hsa-miR-7847-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0563] The 157th target gene is the hsa-miR-4463 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0564] The 158th target gene is the hsa-miR-128-2-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0565] The 159th target gene is the hsa-miR-4508 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0566] The 160th target gene is the hsa-miR-6806-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0567] The 161st target gene is the hsa-miR-7111-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0568] The 162nd target gene is the hsa-miR-6782-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0569] The 163rd target gene is the hsa-miR-4734 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0570] The 164th target gene is the hsa-miR-3162-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0571] The 165th target gene is the hsa-miR-887-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0572] The 166th target gene is the hsa-miR-6752-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0573] The 167th target gene is the hsa-miR-6724-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0574] The 168th target gene is the hsa-miR-23b-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Documents 2 and 3).
[0575] The 169th target gene is the hsa-miR-23a-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0576] The 170th target gene is the hsa-miR-625-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 4).
[0577] The 171st target gene is the hsa-miR-1228-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0578] The 172nd target gene is the hsa-miR-614 gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0579] The 173rd target gene is the hsa-miR-1913 gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 4).
[0580] The 174th target gene is the hsa-miR-92a-2-5p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 1).
[0581] The 175th target gene is the hsa-miR-187-5p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 5).
[0582] The 176th target gene is the hsa-miR-16-5p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Documents 4 and 5).
[0583] The 177th target gene is the hsa-miR-92b-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 1).
[0584] The 178th target gene is the hsa-miR-150-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0585] The 179th target gene is the hsa-miR-564 gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0586] The 180th target gene is the hsa-miR-125a-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 3).
[0587] The 181st target gene is the hsa-miR-92b-5p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 1).
[0588] The 182nd target gene is the hsa-miR-92a-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Documents 1, 4, and 5).
[0589] The 183rd target gene is the hsa-miR-663a gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 4).
[0590] The 184th target gene is the hsa-miR-4688 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0591] The 185th target gene is the hsa-miR-4648 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0592] The 186th target gene is the hsa-miR-6085 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0593] The 187th target gene is the hsa-miR-6126 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0594] The 188th target gene is the hsa-miR-6880-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0595] The 189th target gene is the hsa-miR-328-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0596] The 190th target gene is the hsa-miR-6768-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0597] The 191st target gene is the hsa-miR-3180 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0598] The 192nd target gene is the hsa-miR-6087 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0599] The 193rd target gene is the hsa-miR-1273g-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0600] The 194th target gene is the hsa-miR-1225-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0601] The 195th target gene is the hsa-miR-3196 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0602] The 196th target gene is the hsa-miR-4695-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0603] The 197th target gene is the hsa-miR-6732-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there have been no reports that changes in the expression of this gene or its transcripts can serve as markers for liver cancer.
[0604] The 198th target gene is the hsa-miR-638 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0605] The 199th target gene is the hsa-miR-6813-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0606] The 200th target gene is the hsa-miR-665 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0607] The 201st target gene is the hsa-miR-486-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Documents 2 and 3).
[0608] The 202nd target gene is the hsa-miR-4466 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0609] The 203rd target gene is the hsa-miR-30c-1-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Documents 3 and 5).
[0610] The 204th target gene is the hsa-miR-3621 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0611] The 205th target gene is the hsa-miR-6743-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0612] The 206th target gene is the hsa-miR-4298 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0613] The 207th target gene is the hsa-miR-4741 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0614] The 208th target gene is the hsa-miR-3619-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0615] The 209th target gene is the hsa-miR-6824-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0616] The 210th target gene is the hsa-miR-5698 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0617] The 211th target gene is the hsa-miR-371a-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0618] The 212th target gene is the hsa-miR-4488 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0619] The 213th target gene is the hsa-miR-1233-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0620] The 214th target gene is the hsa-miR-4723-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0621] The 215th target gene is the hsa-miR-24-3p gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0622] The 216th target gene is the hsa-miR-1238-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0623] The 217th target gene is the hsa-miR-4442 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0624] The 218th target gene is the hsa-miR-3928-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0625] The 219th target gene is the hsa-miR-6716-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0626] The 220th target gene is the hsa-miR-6089 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0627] The 221st target gene is the hsa-miR-6124 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for liver cancer.
[0628] The 222nd target gene is the hsa-miR-6778-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0629] The 223rd target gene is the hsa-miR-557 gene, its homologues, its transcription products, or its mutants or derivatives. It has been reported that changes in the expression of this gene or its transcripts can serve as markers for liver cancer (Patent Document 2).
[0630] The 224th target gene is the hsa-miR-6090 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for liver cancer.
[0631] The 225th target gene is the hsa-miR-6757-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0632] The 226th target gene is the hsa-miR-4448 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0633] The 227th target gene is the hsa-miR-671-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0634] The 228th target gene is the hsa-miR-3178 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0635] The 229th target gene is the hsa-miR-4725-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0636] The 230th target gene is the hsa-miR-940 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0637] The 231st target gene is the hsa-miR-6789-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0638] The 232nd target gene is the hsa-miR-4484 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0639] The 233rd target gene is the hsa-miR-4634 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0640] The 234th target gene is the hsa-miR-4745-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0641] The 235th target gene is the hsa-miR-4730 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0642] The 236th target gene is the hsa-miR-6803-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0643] The 237th target gene is the hsa-miR-6798-5p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0644] The 238th target gene is the hsa-miR-3648 gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0645] The 239th target gene is the hsa-miR-4783-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0646] The 240th target gene is the hsa-miR-6836-3p gene, its homologues, its transcription products, or its mutants or derivatives. To date, there has been no report that changes in the expression of genes or their transcripts can serve as markers for liver cancer.
[0647] 2. Nucleic acid probes or primers for liver cancer detection
[0648] In the present invention, a nucleic acid capable of specifically binding to the target nucleic acid as the liver cancer marker described above can be used as a nucleic acid for detecting or diagnosing liver cancer, such as a nucleic acid probe or primer.
[0649] In the present invention, the nucleic acid probe or primer that can be used to detect liver cancer or diagnose liver cancer can qualitatively and / or quantitatively measure the presence, expression level or presence level of the target nucleic acid as the liver cancer marker, such as hsa-miR-1343-3p, 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, 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-6717-5 p, hsa-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-mi R-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, hsa-mi R-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-4665-5p, hsa-m iR-7845-5p, hsa-miR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765-5p, hsa-miR-296-5p, hsa-miR-3675-3p, hsa-miR-6781-5p, hsa-miR-423-5p, hs a-miR-3663-3p, hsa-miR-6784-5p, hsa-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-mi R-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, 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-1915-5p, hsa-miR-3940-5p, hsa-miR-1185-2-3p, hsa-miR-6746-5p, hsa-miR-5001-5p, hsa-miR-1228-5 p、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-6805-3p、hs a-miR-6808-5p, hsa-miR-4449, hsa-miR-1199-5p, hsa-miR-1275, hsa-miR-4792, hsa-miR-4443, hsa-miR-6891-5p, hsa-miR-6826-5p, hsa-miR-68 07-5p、hsa-miR-7150、hsa-miR-4534、hsa-miR-4476、hsa-miR-4649-5p、hsa-miR-4525、hsa-miR-1915-3p、hsa-miR-4516、hsa-miR-4417、hsa-miR -642b-3p、hsa-miR-3141、hsa-miR-5100、hsa-miR-6848-5p、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-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-36 20-5p, 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-1 185-1-3p, hsa-miR-6774-5p, hsa-miR-8059, hsa-miR-3131, hsa-miR-7847-3p, hsa-miR-4463, hsa-miR-128-2-5p, hsa-miR-4508, hsa-miR-6806-5 p, 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-6789-5p, hsa-miR-4484, hsa-miR-4634, hsa-miR-47 hsa-miR-45-5p, 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 a homologue thereof, a transcription product thereof, a mutant or derivative thereof, and hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-625-3p, hsa-miR-1228-3p, 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-miR-125a-3p, hsa-miR-92b-5p, hsa-miR-92a-3p, or hsa-miR-663a, or a combination thereof, or a homologue thereof, a transcription product thereof, a mutant or derivative thereof, and hsa-miR-4688, hsa-miR-4689, or hsa-miR-4681 may be combined with the same as appropriate. 648. hsa-miR-6085, hsa-miR-6126, hsa-miR-6880-5p, hsa-miR-328-5p, hsa-miR-6768-5p, hsa-miR-3180, hsa-miR-60 87. hsa-miR-1273g-3p, hsa-miR-1225-5p, hsa-miR-3196, 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-mi R-4298, 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-4723-5p, 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-557, or hsa-miR-6090, or a combination thereof, or a homologue thereof, a transcription product thereof, a mutant or derivative thereof.
[0650] Regarding the target nucleic acids described above, expression levels in subjects suffering from liver cancer may be increased or decreased (hereinafter referred to as "increased / decreased") depending on the type of target nucleic acid. Therefore, the nucleic acids of the present invention can be used effectively to detect liver cancer by measuring the expression levels of the target nucleic acids in body fluids derived from subjects suspected of suffering from liver cancer (e.g., humans) and in body fluids derived from healthy subjects, and comparing these results.
[0651] The nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of sequence numbers 1 to 167 and 714 to 729, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of sequence numbers 1 to 167 and 714 to 729.
[0652] The nucleic acid probe or primer that can be used in the present invention may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of at least one base sequence represented by SEQ ID NOs: 168 to 183, or a primer for amplifying a polynucleotide consisting of at least one base sequence represented by SEQ ID NOs: 168 to 183.
[0653] The nucleic acid probes or primers that can be used in the present invention may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of at least one base sequence represented by SEQ ID NOs: 184 to 224, or a primer for amplifying a polynucleotide consisting of at least one base sequence represented by SEQ ID NOs: 184 to 224.
[0654] Specifically, the nucleic acid probe or primer comprises a polynucleotide group comprising a base sequence represented by any one of SEQ ID NOs: 1 to 765, or a base sequence in which u is t in the base sequence, and a polynucleotide group complementary thereto; a polynucleotide group and a polynucleotide group complementary thereto that hybridize under stringent conditions (described below) with a DNA consisting of a base sequence complementary to the base sequence; and a polynucleotide group comprising 15 or more, preferably 17 or more, consecutive bases in the base sequence of the polynucleotide group. These polynucleotides can be used as nucleic acid probes and primers for detecting the liver cancer markers described above as target nucleic acids.
[0655] More specifically, examples of nucleic acid probes or primers that can be used in the present invention include one or more polynucleotides selected from the following polynucleotides (a) to (e).
[0656] (a) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0657] (b) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729,
[0658] (c) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0659] (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, and
[0660] (e) A polynucleotide that hybridizes to any one of the polynucleotides (a) to (d) above under stringent conditions.
[0661] The nucleic acid probe or primer that can be used in the present invention may further contain a polynucleotide selected from the polynucleotides shown in the following (f) to (j), in addition to at least one polynucleotide selected from the polynucleotides (a) to (e) above.
[0662] (f) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0663] (g) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 168 to 183,
[0664] (h) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0665] (i) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, and
[0666] (j) A polynucleotide that hybridizes to any one of the polynucleotides (f) to (i) above under stringent conditions.
[0667] The nucleic acid probe or primer that can be used in the present invention may further contain a polynucleotide selected from the polynucleotides shown in the following (k) to (o), in addition to at least one polynucleotide selected from the polynucleotides (a) to (j) above.
[0668] (k) a polynucleotide consisting of the base sequence represented by any of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0669] (1) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 184 to 224,
[0670] (m) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, a variant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide comprising 15 or more consecutive bases,
[0671] (n) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, and
[0672] (o) A polynucleotide that hybridizes to any one of the polynucleotides (k) to (n) above under stringent conditions.
[0673] The "fragment of the polynucleotide comprising 15 or more consecutive bases" in the above-mentioned polynucleotide may include, for example, a consecutive number of bases in the base sequence of each polynucleotide ranging from 15 to less than the total number of bases in the sequence, from 17 to less than the total number of bases in the sequence, from 19 to less than the total number of bases in the sequence, etc., but is not limited thereto.
[0674] Any of the aforementioned polynucleotides or fragments thereof used in the present invention may be DNA or RNA.
[0675] The polynucleotides that can be used in the present invention can be produced using common techniques such as DNA recombination technology, PCR, and methods using a DNA / RNA automatic synthesizer.
[0676] For DNA recombination technology and PCR method, for example, the techniques described in Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989) and the like can be used.
[0677] Human-derived hsa-miR-1343-3p, 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, 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-miR-6816-5p, hsa-miR-4281, hsa-miR-6729-5p, hsa-miR-8069, hsa-miR-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, hsa-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-4665-5p, hsa-miR-7845-5p, hsa-miR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765-5p, hsa-miR-296-5p, hsa-miR-3675-3p, 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-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, as shown by serial numbers 1 to 224 and 714 to 729hsa-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-mi R-1229-5p, hsa-miR-6820-5p, hsa-miR-6777-5p, hsa-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-4467, hsa-miR-4419b, hsa-miR-1914-3p, hsa-miR-4632-5p, hsa-miR-1915-5p, hsa-miR-3940-5p, h sa-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-6799-5p, hsa-miR-6861-5p, hsa-miR-6727-5p, hsa-miR-4513, hsa-miR-6805-3p, hsa-miR-6808-5p, hsa-miR-4449, hsa-miR-1199-5p, hsa-miR-1275, hsa-m iR-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-1915-3p, hsa-miR-4516, hsa-miR-4417, hsa-miR-642b-3p, hsa-miR-3141, hsa-miR-5100, hsa-miR-6848-5p, hsa-miR-47 39, 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-1343-5phsa-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-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-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、h sa-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-m iR-940, hsa-miR-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, hs a-miR-4783-3p, hsa-miR-6836-3p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-625-3p, hsa-miR-1228-3p, hsa-miR-614, hsa-miR-1913, hsa-miR-9 2a-2-5p、hsa-miR-187-5p、hsa-miR-16-5p、hsa-miR-92b-3p、hsa-miR-15 0-3p、hsa-miR-564、hsa-miR-125a-3p、hsa-miR-92b-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, hsa-miR-1273g-3p, h sa-miR-1225-5p, hsa-miR-3196, hsa-miR-4695-5p, hsa-miR-6732-5p, hsa-miR-638, hsa-mi R-6813-5p, hsa-miR-665, hsa-miR-486-3p, hsa-miR-4466, hsa-miR-30c-1-3p, hsa-miR-362 1. hsa-miR-6743-5p, hsa-miR-4298, hsa-miR-4741, hsa-miR-3619-3p, hsa-miR-6824-5p, hs a-miR-5698, hsa-miR-371a-5p, hsa-miR-4488, hsa-miR-1233-5p, hsa-miR-4723-5p, hsa-mi 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-557, and hsa-miR-6090 are known, and methods for obtaining them are also known as described above. Therefore, by cloning these genes, polynucleotides that can be used as nucleic acid probes or primers in the present invention can be prepared.
[0678] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. This synthesis generally uses the phosphoramidite method, which allows the automatic synthesis of single-stranded DNA of up to about 100 bases. Automated DNA synthesizers are commercially available from companies such as Polygen, ABI, and Applied BioSystems.
[0679] Alternatively, the polynucleotide of the present invention can also be prepared by cDNA cloning. For example, the cDNA cloning technique can utilize the microRNA Cloning Kit (Wako).
[0680] Here, the sequences of nucleic acid probes and primers for detecting a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 224 and 714 to 729 do not exist in vivo as miRNA or its precursor. For example, the base sequences represented by SEQ ID NOs: 1 and 131 are generated from the precursor represented by SEQ ID NO: 225, but the precursor has Figure 1 In the hairpin-like structure shown, the base sequences shown in SEQ ID NO: 1 and SEQ ID NO: 131 have mismatches. Therefore, base sequences completely complementary to the base sequences shown in SEQ ID NO: 1 or SEQ ID NO: 131 do not naturally occur in vivo. Similarly, nucleic acid probes and primers used to detect the base sequences shown in any of SEQ ID NOs: 1 to 224 and 714 to 729 have artificial base sequences that do not exist in vivo.
[0681] 3. Kits or devices for liver cancer detection
[0682] The present invention also provides a kit or device for detecting liver cancer that contains one or more polynucleotides (which may include mutants, fragments or derivatives; hereinafter sometimes referred to as detection polynucleotides) for measuring target nucleic acids that serve as liver cancer markers and can be used as nucleic acid probes or primers in the present invention.
[0683] The target nucleic acid as a liver cancer marker in the present invention is preferably selected from the following group 1:
[0684] miR-1343-3p, 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-6787-5 p、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-8 072, 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-190 8-5p、miR-6840-3p、miR-6765-5p、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-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-68 45-5p、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-6877-5 p、miR-1225-3p、miR-6088、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, 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, mi R-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, m iR-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-3648miR-4783-3p and miR-6836-3p.
[0685] Depending on the situation, the additional target nucleic acids that can be used for determination are preferably selected from the following group 2: 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 and miR-663a.
[0686] The additional target nucleic acid that can be used for the measurement as needed is preferably selected from the following group 3: 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, 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-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.
[0687] The kit or device of the present invention comprises a nucleic acid capable of specifically binding to the target nucleic acid as the liver cancer marker, preferably the nucleic acid probe or primer described in 2 above, specifically one or more polynucleotides selected from the polynucleotides described in 2 above or their mutants.
[0688] Specifically, the kit or device of the present invention may contain at least one or more of the following: a polynucleotide comprising a base sequence represented by any one of sequence numbers 1 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence (or consisting of a base sequence represented by any one of sequence numbers 1 to 235 and 851 to 856, or a base sequence in which u is t in the base sequence), a polynucleotide comprising a complementary sequence thereof (or consisting of a complementary sequence thereof), a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising 15 or more consecutive bases.
[0689] The kit or device of the present invention may further include one or more of the following: a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 168 to 183 or a base sequence in which u is t in the base sequence (or consisting of a base sequence represented by any one of SEQ ID NOs: 168 to 183 or a base sequence in which u is t in the base sequence), a polynucleotide comprising a complementary sequence thereof (or consisting of a complementary sequence thereof), a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising 15 or more consecutive bases.
[0690] The kit or device of the present invention may further include one or more of the following: a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 184 to 224 or a base sequence in which u is t in the base sequence (or consisting of the base sequence represented by any one of SEQ ID NOs: 184 to 224 or a base sequence in which u is t in the base sequence), a polynucleotide comprising (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising 15 or more consecutive bases.
[0691] The fragments that can be included in the kit or device of the present invention are, for example, one or more, preferably two or more, polynucleotides selected from the following (1) to (3).
[0692] (1) A polynucleotide comprising 15 or more consecutive bases in a base sequence in which u is t in any one of SEQ ID NOs: 1 to 167 and 714 to 729 or a complementary sequence thereof.
[0693] (2) A polynucleotide comprising 15 or more consecutive bases in a base sequence in which u is t in any one of SEQ ID NOs: 168 to 183 or a complementary sequence thereof.
[0694] (3) A polynucleotide comprising 15 or more consecutive bases in a base sequence in which u is t in any one of SEQ ID NOs: 184 to 224 or a complementary sequence thereof.
[0695] In a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 1 to 167 and 714 to 729 or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0696] In addition, in a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 168 to 183 or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0697] In addition, in a preferred embodiment, the above-mentioned polynucleotide is a polynucleotide composed of a base sequence shown in any one of sequence numbers 184 to 224 or a base sequence in which u is t in the base sequence; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant thereof containing more than 15, preferably more than 17, and more preferably more than 19 consecutive bases.
[0698] In a preferred embodiment, the fragment may be a polynucleotide comprising 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0699] In the present invention, the fragment size of a polynucleotide is, for example, a continuous number of bases ranging from 15 to less than the total number of bases in the base sequence of each polynucleotide, from 17 to less than the total number of bases in the sequence, from 19 to less than the total number of bases in the sequence, etc.
[0700] As a combination of the above-mentioned polynucleotides constituting the kit or device of the present invention, specifically, any combination of the above-mentioned polynucleotides consisting of the base sequences represented by the sequence numbers shown in Table 1 (sequence numbers 1 to 224 and 714 to 729 corresponding to the miRNA markers in Table 1) or their complementary sequences can be cited. These are strictly illustrative, and all other possible combinations are included in the present invention.
[0701] For example, in the present invention, as the above-mentioned combination constituting a kit or device for distinguishing liver cancer from healthy bodies, it is expected that the above-mentioned polynucleotides composed of the base sequences represented by the sequence numbers shown in Table 1 are combined in two or more combinations. Usually, a combination of two can obtain sufficient performance.
[0702] Specifically, as a combination of two polynucleotides consisting of a base sequence or its complementary sequence for distinguishing liver cancer from healthy bodies, a combination of two of the above-mentioned polynucleotides consisting of the base sequences represented by sequence numbers 1 to 224 and 714 to 729 is preferably a combination containing at least one newly discovered polynucleotide consisting of the base sequences represented by sequence numbers 1 to 167 and 714 to 729.
[0703] In addition, as a combination of cancer type-specific polynucleotides that can distinguish not only liver cancer from healthy individuals but also liver cancer from other cancers, preferably, for example, a polynucleotide selected from SEQ ID NOs: 1, 2, 3, 5, 7, 9, 12, 17, 20, 22, 27, 28, 29, 38, 39, 44, 46, 48, 51, 54, 61, 76, 89, 93, 101, 109, 116, 123, 132, 134, 136, 148, 150, 151, 155, 157, 164, 166, A group of polynucleotides consisting of the base sequences shown in 167, 172, 180, 186, 188, 189, 197, 198, 214, 216, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728 and 729, or their complementary sequences (hereinafter referred to as "cancer type-specific polynucleotide group 1"), and a combination of multiple polynucleotides consisting of other sequence numbers.
[0704] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish not only liver cancer from healthy individuals but also liver cancer from other cancers, a combination of multiple polynucleotides selected from the cancer type-specific polynucleotide group 1 is more preferred.
[0705] Furthermore, as a combination of cancer type-specific polynucleotides that can distinguish not only liver cancer from healthy bodies but also liver cancer from other cancers, among the combinations of multiple polynucleotides selected from cancer type-specific polynucleotide group 1, it is more preferable to be a combination of polynucleotides in a group consisting of polynucleotides consisting of base sequences or their complementary sequences shown in sequence numbers 1, 3, 7, 9, 22, 38, 44, 134, 148, 155, 157, 164, 167, 172, 214, 714, 715, 716 and 717 contained in cancer type-specific polynucleotide group 1 (hereinafter referred to as "cancer type-specific polynucleotide group 2").
[0706] The number of combinations of the above-mentioned cancer type-specific polynucleotides can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or a combination of 10 or more, more preferably a combination of 4 or more. Usually, sufficient performance can be obtained with a combination of 4.
[0707] The following non-limiting examples include combinations of a polynucleotide consisting of the base sequence represented by SEQ ID NO: 1 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by SEQ ID NO: 1 or its complementary sequence represented by the sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0708] (1) Combination of SEQ ID NOs: 1, 7, 9, and 148 (markers: hsa-miR-1343-3p, hsa-miR-6131, hsa-miR-7641, and hsa-miR-642a-3p)
[0709] (2) Combination of SEQ ID NOs: 1, 9, 155, and 172 (markers: hsa-miR-1343-3p, hsa-miR-7641, hsa-miR-3131, and hsa-miR-614)
[0710] (3) Combination of SEQ ID NOs: 1, 9, 148, and 155 (markers: hsa-miR-1343-3p, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-3131)
[0711] (4) Combination of SEQ ID NOs: 1, 155, 172, and 715 (markers: hsa-miR-1343-3p, hsa-miR-3131, hsa-miR-614, and hsa-miR-4448)
[0712] (5) Combination of SEQ ID NOs: 1, 155, 164, and 715 (markers: hsa-miR-1343-3p, hsa-miR-3131, hsa-miR-3162-5p, and hsa-miR-4448)
[0713] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 3 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by sequence number or its complementary sequence represented by sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0714] (1) Combination of SEQ ID NOs: 3, 7, 9, and 148 (markers: hsa-miR-6515-3p, hsa-miR-6131, hsa-miR-7641, and hsa-miR-642a-3p)
[0715] (2) Combination of SEQ ID NOs: 3, 22, 27, and 46 (markers: hsa-miR-6515-3p, hsa-miR-663b, hsa-miR-6729-5p, and hsa-miR-1908-5p)
[0716] (3) Combination of SEQ ID NOs: 1, 3, 29, and 155 (markers: hsa-miR-1343-3p, hsa-miR-6515-3p, hsa-miR-4706, and hsa-miR-3131)
[0717] (4) Combination of SEQ ID NOs: 1, 3, 151, and 155 (markers: hsa-miR-1343-3p, hsa-miR-6515-3p, hsa-miR-5195-3p, and hsa-miR-3131)
[0718] (5) Combination of SEQ ID NOs: 3, 7, 148, and 715 (markers: hsa-miR-6515-3p, hsa-miR-6131, hsa-miR-642a-3p, and hsa-miR-4448)
[0719] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 7 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by sequence number or its complementary sequence represented by sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0720] (1) Combination of SEQ ID NOs: 7, 28, 148, and 717 (markers: hsa-miR-6131, hsa-miR-8069, hsa-miR-642a-3p, and hsa-miR-3178)
[0721] (2) Combination of SEQ ID NOs: 7, 9, 148, and 186 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-6085)
[0722] (3) Combination of SEQ ID NOs: 7, 148, 172, and 715 (markers: hsa-miR-6131, hsa-miR-642a-3p, hsa-miR-614, and hsa-miR-4448)
[0723] (4) Combination of SEQ ID NOs: 7, 9, 148, and 723 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-4745-5p)
[0724] (5) Combination of SEQ ID NOs: 7, 9, 28, and 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-8069, and hsa-miR-642a-3p)
[0725] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 9 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by sequence number or its complementary sequence represented by sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0726] (1) Combination of SEQ ID NOs: 7, 9, 148, and 157 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-4463)
[0727] (2) Combination of SEQ ID NOs: 7, 9, 148, and 722 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-4634)
[0728] (3) Combination of SEQ ID NOs: 7, 9, 27, and 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-6729-5p, and hsa-miR-642a-3p)
[0729] (4) Combination of SEQ ID NOs: 7, 9, 148, and 725 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-6803-5p)
[0730] (5) Combination of SEQ ID NOs: 7, 9, 148, and 729 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, and hsa-miR-6836-3p)
[0731] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 22 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by sequence number or its complementary sequence represented by sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0732] (1) Combination of SEQ ID NOs: 7, 9, 22, and 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-663b, and hsa-miR-642a-3p)
[0733] (2) Combination of SEQ ID NOs: 7, 22, 28, and 148 (markers: hsa-miR-6131, hsa-miR-663b, hsa-miR-8069, and hsa-miR-642a-3p)
[0734] (3) Combination of SEQ ID NOs: 7, 22, 148, and 189 (markers: hsa-miR-6131, hsa-miR-663b, hsa-miR-642a-3p, and hsa-miR-328-5p)
[0735] (4) Combination of SEQ ID NOs: 2, 7, 22, and 148 (markers: hsa-miR-6726-5p, hsa-miR-6131, hsa-miR-663b, and hsa-miR-642a-3p)
[0736] (5) Combination of SEQ ID NOs: 7, 22, 148, and 720 (markers: hsa-miR-6131, hsa-miR-663b, hsa-miR-642a-3p, and hsa-miR-6789-5p)
[0737] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 38 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by the sequence number represented by the sequence number of three polynucleotides selected from the cancer type-specific polynucleotide group 1 or its complementary sequence.
[0738] (1) Combination of SEQ ID NOs: 7, 9, 38, and 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-3622a-5p, and hsa-miR-642a-3p)
[0739] (2) Combination of SEQ ID NOs: 7, 38, 51, and 148 (markers: hsa-miR-6131, hsa-miR-3622a-5p, hsa-miR-6781-5p, and hsa-miR-642a-3p)
[0740] (3) Combination of SEQ ID NOs: 7, 38, 148, and 718 (markers: hsa-miR-6131, hsa-miR-3622a-5p, hsa-miR-642a-3p, and hsa-miR-4725-3p)
[0741] (4) Combination of SEQ ID NOs: 7, 38, 148, and 216 (markers: hsa-miR-6131, hsa-miR-3622a-5p, hsa-miR-642a-3p, and hsa-miR-1238-5p)
[0742] (5) Combination of SEQ ID NOs: 7, 38, 148, and 728 (markers: hsa-miR-6131, hsa-miR-3622a-5p, hsa-miR-642a-3p, and hsa-miR-4783-3p)
[0743] Furthermore, the following non-limiting examples include a combination of a polynucleotide consisting of the base sequence represented by sequence number 44 or its complementary sequence, and a polynucleotide consisting of the base sequence represented by sequence number or its complementary sequence represented by sequence numbers of three polynucleotides selected from cancer type-specific polynucleotide group 1.
[0744] (1) Combination of SEQ ID NOs: 7, 9, 44, and 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-4665-5p, and hsa-miR-642a-3p)
[0745] (2) Combination of SEQ ID NOs: 7, 44, 123, and 148 (markers: hsa-miR-6131, hsa-miR-4665-5p, hsa-miR-4739, and hsa-miR-642a-3p)
[0746] (3) Combination of SEQ ID NOs: 7, 38, 44, and 148 (markers: hsa-miR-6131, hsa-miR-3622a-5p, hsa-miR-4665-5p, and hsa-miR-642a-3p)
[0747] (4) Combination of S...
Claims
1. Use of a nucleic acid that can specifically bind to a polynucleotide of hsa-miR-1343-3p, which is a liver cancer marker, for manufacturing a kit for detecting liver cancer or a device for detecting liver cancer, The nucleic acid is a polynucleotide selected from the polynucleotides shown in (a) to (b) below, (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 1 or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases, and (b) A polynucleotide consisting of a base sequence complementary to the base sequence shown in SEQ ID NO: 1 or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases.
2. The use according to claim 1, wherein further used are those capable of being combined with, as other liver cancer markers, selected from 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, 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-miR-6816-5p, hsa-miR-4281, hsa-miR-6729-5p, hsa-miR-8069, hsa-miR-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, hsa-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-4665-5p, hsa-miR-7845-5p, hsa-miR-1908-5p, hsa-miR-6840-3p, hsa-miR-6765-5p, hsa-miR-296-5p, hsa-miR-3675-3p, 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-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-3185hsa-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-1229-5p, hsa -miR-6820-5p, hsa-miR-6777-5p, hsa-miR-3917, hsa-miR-5787, hsa-miR-4286, hsa-miR-6877-5p, hsa-miR-1225-3p, hsa-miR-6088, hsa-miR-680 0-5p, 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, and 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-6799-5p, and hsa-miR-6861-5p hsa-miR-6727-5p, hsa-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-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, hs a-miR-1915-3p, hsa-miR-4516, hsa-miR-4417, hsa-miR-642b-3p, hsa-miR-3141, hsa-miR-5100, hsa-miR-6848-5p, 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-6510-5p, hsa-miR-1343-5p, and hsa-miR-1247-3phsa-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-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-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, 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-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-4783-3p and hsa-miR-6836-3p, and / or hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-625-3p, hsa-miR-1228-3p, 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-miR-125a-3p, hsa-miR-92b-5p, hsa-miR-92a-3p, hsa-miR-663aA nucleic acid that specifically binds to at least one polynucleotide among 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-1273g-3p, hsa-miR-1225-5p, hsa-miR-3196, 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-4298, 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-4723-5p, 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-557, and hsa-miR-6090.
3. The use according to claim 2, wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in the following (a') to (b'), and / or a polynucleotide selected from the polynucleotides shown in the following (c) to (f), (a′) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 2 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases, and (b′) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 2 to 167 and 714 to 729, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases; (c) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (d) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 168 to 183, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases, (e) a polynucleotide consisting of the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases, and (f) A polynucleotide consisting of a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 184 to 224, or a base sequence in which u is t in the base sequence, or a fragment of the polynucleotide comprising 15 or more consecutive bases.
4. The use according to any one of claims 1 to 3, which is use of at least two or more nucleic acids capable of specifically binding to at least two or more polynucleotides selected from all liver cancer markers described in claim 1 or 2. The use according to claim 1 , wherein the liver cancer is human liver cancer.
Citation Information
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