Detection kit or device and detection method for liver cancer

Abstract

The invention provides a kit or device for detecting liver cancer, and a detection method. The present invention relates to a kit or device for detecting liver cancer comprising a nucleic acid capable of specifically binding to miRNA in a specimen of a subject, and a method for detecting liver cancer comprising measuring the miRNA in vitro.

Description

[0001] This application is a divisional application of patent application filed on June 18, 2015, with application number 201580032544.9 and entitled "Detection kit or device for liver cancer and detection method". Technical Field

[0002] This invention relates to a kit or apparatus for detecting liver cancer, comprising a nucleic acid capable of specifically binding to a specific miRNA, for examining whether a subject has liver cancer, and a method for detecting liver cancer comprising using the nucleic acid to determine the expression level of the miRNA. Background Technology

[0003] The liver, located in the upper right abdomen, is the largest organ in the body. Its main functions are the metabolism of nutrients and the detoxification and excretion of harmful substances. According to statistics on cancers in various parts of the body published by the Cancer Countermeasures Information Center of the National Cancer Center of the National Research and Development Corporation in Japan in 2011, the number of people diagnosed with liver cancer was 47,271, which means that one in 35 Japanese people suffers from 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, both men and women, rose to 30,690, making it the fourth most common cancer site in terms of mortality. In addition, it is said that in the United States, the estimated number of people diagnosed with liver cancer in 2014 also rose to 33,190, with approximately 23,000 deaths (Non-Patent Literature 1).

[0004] Generally speaking, primary liver cancer often refers to hepatocellular carcinoma, which accounts for about 80% of all liver cancers. In addition, there are rarer types of cancer, such as intrahepatic cholangiocarcinoma and bile duct cystic adenocarcinoma, which account for 10% to 20% of all primary liver cancers.

[0005] In Non-Patent Literature 2, the progression of liver cancer is defined as hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Here, hepatocellular carcinoma, in particular, is classified into stages I (T1 / N0 / M0), II (T2 / N0 / M0), IIIA (T3a / N0 / M0), IIIB (T3b / N0 / M0), IIIC (T4 / N0 / M0), IVA (N1 / M0), and IVB (M1) based on the degree of tumor spread (T0-4), lymph node metastasis (N0, N1), and distant metastasis (M0, M1).

[0006] The 5-year relative survival rate for liver cancer varies depending on the stage of progression. According to non-patent literature 1, the rate is reported to be 28% for cancer confined to the liver (stages 1, 2, and some stages 3), 7% for cancers confirmed to have metastasized to nearby areas of the liver (stages IIIC and IVA), and 2% for cancers confirmed to have metastasized to distant sites (stage IVB). Therefore, early detection and treatment of liver cancer before metastasis is confirmed can significantly improve survival rates.

[0007] Treatment for liver cancer primarily involves three methods: surgical treatment (mainly resection and liver transplantation); local therapy (injecting drugs or cauterizing via biopsy to eradicate the cancer); and hepatic artery embolization, often combined with drug therapy and radiation therapy. Partial resection of the liver is often used to cure early-stage liver cancer when it is not readily apparent in blood vessels or surrounding areas (Non-Patent Literature 1). On the other hand, even if the cancer is localized but cannot be resected due to its large diameter or proximity to blood vessels, liver transplantation is considered. If metastasis is further confirmed, systemic drug therapy and radiation therapy are then administered (Non-Patent Literature 1).

[0008] As described in Non-Patent Literature 1, a single examination for liver cancer includes visual inspection, palpation, and imaging examinations such as ultrasound, CT, MRI, and angiography. Furthermore, tumor markers used for liver cancer detection, such as AFP (alpha-fetoprotein) and PIVKA-II, are often used in conjunction with ultrasound. If a suspicion of liver cancer is found based on these single examinations, a second examination is performed—a pathological examination where cells and tissues are collected by inserting a needle into the lesion and studied under a microscope.

[0009] On the other hand, it is known that the most important cause of liver cancer is long-term infection with hepatitis B and hepatitis C viruses. Therefore, in cases where liver cancer is suspected, in addition to the above-mentioned examination, hepatitis virus testing is sometimes performed.

[0010] Although it is in the research stage, as shown in Patent Documents 1-5, there are reports of methods for detecting liver cancer using the expression levels of microRNAs (miRNAs) in biological samples, such as blood and liver tissue.

[0011] 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 biomarkers.

[0012] Patent document 2 reports the following method: 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 circulating vesicles in body fluids as biomarkers to diagnose various cancers.

[0013] Patent document 3 discloses a method for detecting various diseases including liver cancer by using miRNAs such as hsa-miR-23b-3p, hsa-miR-30c-1-3p, hsa-miR-125a-3p, and hsa-miR-486-3p from tissues and body fluids as biomarkers.

[0014] Patent document 4 discloses a method for detecting various pathological conditions including liver cancer by 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 circulating vesicles in body fluids as biomarkers.

[0015] 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 biomarkers for colorectal cancer, liver cancer, and lung cancer.

[0016] Existing technical documents

[0017] Patent documents

[0018] Patent Document 1: International Publication No. 2010 / 123043

[0019] Patent Document 2: U.S. Patent Application Publication No. 2011 / 003704

[0020] Patent Document 3: International Publication No. 2010 / 054386

[0021] Patent Document 4: International Publication No. 2012 / 174282

[0022] Patent Document 5: International Publication No. 2011 / 076142

[0023] Non-patent literature

[0024] Non-patent literature 1: American Cancer Society, “Liver Cancer”, 2013, pp. 5–8, 14–15, 17–23, 27–41

[0025] Non-patent literature 2: Sobin, L. et al., “TNM Classification of Malignant Tumours, 7th Edition”, 2010, pp. 104-107

[0026] Non-patent literature 3: HCCN Guidelines "Hepatobiliary Cancer, 2nd Edition", 2014, MS-4

[0027] Non-patent literature 4: Zhang, B. and Yang, B., 1999, Journal of Medical Screening, Vol. 6(2), pp. 108-110

[0028] Non-patent literature 5: Takahashi, A. et al., World Journal of Gastroenterology, 2008, Vol. 14(1), pp. 129-31 Summary of the Invention

[0029] The problem that the invention aims to solve

[0030] The objective of this invention is to find new tumor markers for liver cancer and to provide a method for effectively detecting liver cancer using nucleic acids that can specifically bind to these markers.

[0031] Because liver cancer progresses without symptoms, it is difficult to detect early. Furthermore, most of the liver is located within the right rib cage, making palpation difficult. Currently, no effective screening method for liver cancer has been established for the general population without hepatitis virus infection, cirrhosis, or other liver cancer risks (Non-Patent Literature 1). Ultrasound examination is a widely used method for liver cancer screening due to its low burden on patients and simplicity; however, it can be difficult to detect depending on the location of the cancer, and the results are highly dependent on the technician's skill. Therefore, it is hoped that it can be used in conjunction with tumor markers (Non-Patent Literature 3). AFP is known as a tumor marker for liver cancer detection, but when elevated AFP is confirmed, the liver cancer has often progressed, becoming unresectable or metastasizing outside the liver (Non-Patent Literature 1). Furthermore, some liver cancers have been reported not to produce AFP; on the other hand, AFP is known to rise even in cancers other than liver cancer, such as testicular and ovarian cancer, and further in non-cancerous liver diseases, such as persistent hepatitis virus infection. Therefore, it is considered a marker with low specificity (Non-Patent Literature 1). For example, if other cancers are misdiagnosed as liver cancer, the appropriate treatment opportunity is missed, or unnecessary economic and physical burdens are imposed on patients due to the use of incorrect medical treatment. Furthermore, according to the results of a large-scale screening study involving hepatitis B-infected individuals and patients with persistent hepatitis (Non-Patent Literature 4), the detection sensitivity of liver cancer using the AFP test is only 69%, which is insufficient for use as a liver cancer screening test. In addition, while CT and MRI scans can detect liver cancer with high performance, they require specialized equipment and are expensive, thus making them unsuitable for widespread use as a single examination.

[0032] Furthermore, although it is still in the research stage, there are reports such as using the expression level of microRNA (miRNA) in biological samples, represented by blood, to identify liver cancer, but none of them have been put into practical use.

[0033] 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 as miRNAs from blood cells and tissues as biomarkers. However, this detection method requires surgical tissue removal to obtain a sample, which places a heavy physical burden on the patient, making it an undesirable method. Furthermore, Patent Document 1 does not describe the specific accuracy, sensitivity, specificity, or other performance characteristics of this detection method for identifying liver cancer, lacking industrial applicability.

[0034] 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 circulating vesicles in bodily fluids, as biomarkers. However, Patent Document 2 does not describe a specific diagnostic method for liver cancer using this detection method, nor does it describe the accuracy, sensitivity, specificity, or other performance characteristics of the detection method for liver cancer, thus lacking industrial applicability.

[0035] 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 from tissues and body fluids as biomarkers. However, this detection method is based on experimental results from a mouse model, and its effectiveness in detecting liver cancer in humans is unclear. Furthermore, Patent Document 3 does not describe the accuracy, sensitivity, or specificity of its detection performance in identifying liver cancer, thus lacking industrial applicability.

[0036] Patent Document 4 discloses 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 circulating vesicles in body fluids as biomarkers. However, Patent Document 4 does not describe a specific diagnostic method for liver cancer using this detection method. Furthermore, the aforementioned miRNA biomarkers have not been validated in an independent sample group, thus lacking reliability.

[0037] 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 biomarkers for colorectal cancer, liver cancer, and lung cancer. However, these biomarkers are used to distinguish between the colorectal cancer group and the group consisting of liver cancer, lung cancer, and healthy individuals, and are not biomarkers for detecting liver cancer.

[0038] Thus, in the detection of liver cancer, existing tumor markers have low performance. Furthermore, the performance and detection methods for markers in the research stage are not specifically described. Therefore, using them carries the following risks: unnecessary additional testing due to misdiagnosing healthy individuals as liver cancer patients, and missed treatment opportunities due to overlooking liver cancer patients. In addition, measuring miRNAs, which consist of dozens to hundreds of molecules, increases testing costs, making it difficult to use for large-scale screenings such as health diagnostics. Moreover, collecting liver tissue for tumor marker measurement is highly invasive and undesirable for patients. Therefore, there is a need for liver cancer markers that can be detected through low-invasive blood collection and have high accuracy in correctly identifying liver cancer patients and healthy individuals. In particular, early detection and treatment of liver cancer can improve survival rates, and many cases are cured by partial hepatectomy. Therefore, there is a strong desire for highly sensitive liver cancer markers that can detect even low-progression liver cancer.

[0039] Methods for solving problems

[0040] In order to solve the above-mentioned problems, the inventors conducted in-depth research and found that by finding multiple genes that can be used as biomarkers for liver cancer detection from blood that can be collected in a low-invasive manner, and using nucleic acids that can specifically bind to them, liver cancer can be significantly detected, thus completing the present invention.

[0041] <Summary of the Invention>

[0042] That is, the present invention has the following features.

[0043] (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-6798-5pNucleic acids that specifically bind to at least one polynucleotide from miR-3648, miR-4783-3p, and miR-6836-3p.

[0044] (2) According to the kit described in (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, 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, mi 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-470. 6. miR-7108-5p is hsa-miR-7108-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6857-5p is hsa-miR-6857-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6741-5p is hsa-miR-6741-5p, miR-451a is hsa-miR-451a, miR-8063 is hsa-miR-8063, and miR-3622a-5p is 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, miR-4746 -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, miR-1260a is hsa-m 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, 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, miR-4327 The following are listed: hsa-miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, and miR-1199-5p. 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-miR-4649-5p.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, 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 The values ​​are hsa-miR-4492, hsa-miR-1469, hsa-miR-1268b, hsa-miR-6858-5p, hsa-miR-6858-5p, hsa-miR-3937, hsa-miR-939-5p, hsa-miR-939-5p, hsa-miR-3656, hsa-miR-3656, hsa-miR-744-5p, hsa-miR-744-5p, hsa-miR-4687-3p, hsa-miR-4687-3p, hsa-miR-4763-3p, and hsa-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 The values ​​are hsa-miR-4634, miR-4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p, and miR-6836-3p.

[0045] (3) The kit according to (1) or (2), wherein the above nucleic acid is a polynucleotide selected from the polynucleotides shown in (a) to (e) below,

[0046] (a) A polynucleotide consisting of 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, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0047] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–167 and 714–729.

[0048] (c) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 1-167 and 714-729, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0049] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 1–167 and 714–729, or a base sequence in which u is t.

[0050] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.

[0051] (4) The kit according to any one of (1) to (3), wherein the kit further comprises a nucleic acid capable of specifically binding to at least one polynucleotide selected from 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 as other liver cancer markers.

[0052] (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-23b-3p. -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.

[0053] (6) The kit according to (4) or (5), wherein the above nucleic acid is a polynucleotide selected from the polynucleotides shown in (f) to (j) below,

[0054] (f) A polynucleotide consisting of the base sequence shown in any of the sequence numbers 168 to 183, or a sequence of bases in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0055] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 168–183.

[0056] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 168-183 or the base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0057] (i) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequences 168–183 or a base sequence in which u is t, and

[0058] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.

[0059] (7) The kit according to any one of (1) to (6), wherein the kit further comprises a reagent capable of reacting 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- Nucleic acids specifically bound to at least one of the following polynucleotides: 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.

[0060] (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-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-miR-4488, 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, and miR-6778-5p is hsa-miR-6778-5p.miR-557 is hsa-miR-557 and miR-6090 is hsa-miR-6090.

[0061] (9) The kit according to (7) or (8), wherein the above nucleic acid is a polynucleotide selected from the polynucleotides shown in (k) to (o) below,

[0062] (k) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 184 to 224, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0063] (l) A polynucleotide containing the base sequence shown in any of the sequence numbers 184 to 224.

[0064] (m) A polynucleotide, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases, consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 184 to 224 or a base sequence in which u is t.

[0065] (n) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequence numbers 184–224 or a base sequence in which u is t, and

[0066] (o) is a polynucleotide that hybridizes with any of the polynucleotides (k) to (n) above under strict conditions.

[0067] (10) The kit according to any one of (1) to (9), wherein the kit contains at least two nucleic acids capable of specifically binding to at least two polynucleotides selected from all liver cancer markers described in (1) or (2).

[0068] (11) Device for detecting liver cancer, comprising a substance that can bind to any of the following liver cancer markers 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-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-6798-5pNucleic acids that specifically bind to at least one polynucleotide from miR-3648, miR-4783-3p, and miR-6836-3p.

[0069] (12) The apparatus 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, 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, mi 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-470. 6. miR-7108-5p is hsa-miR-7108-5p, miR-4433b-3p is hsa-miR-4433b-3p, miR-6893-5p is hsa-miR-6893-5p, miR-6857-5p is hsa-miR-6857-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6741-5p is hsa-miR-6741-5p, miR-451a is hsa-miR-451a, miR-8063 is hsa-miR-8063, and miR-3622a-5p is 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, miR-4746 -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, miR-1260a is hsa-m 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, 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, miR-4327 The following are listed: hsa-miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, and miR-1199-5p. 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-miR-4649-5p.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, 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 The values ​​are hsa-miR-4492, hsa-miR-1469, hsa-miR-1268b, hsa-miR-6858-5p, hsa-miR-6858-5p, hsa-miR-3937, hsa-miR-939-5p, hsa-miR-939-5p, hsa-miR-3656, hsa-miR-3656, hsa-miR-744-5p, hsa-miR-744-5p, hsa-miR-4687-3p, hsa-miR-4687-3p, hsa-miR-4763-3p, and hsa-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 The values ​​are hsa-miR-4634, miR-4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p, and miR-6836-3p.

[0070] (13) The apparatus according to (11) or (12), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in (a) to (e) below.

[0071] (a) A polynucleotide consisting of 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, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0072] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–167 and 714–729.

[0073] (c) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 1-167 and 714-729, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0074] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 1–167 and 714–729, or a base sequence in which u is t.

[0075] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.

[0076] (14) The device according to any one of (11) to (13), wherein the device further comprises a nucleic acid capable of specifically binding to at least one polynucleotide selected from 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 as other liver cancer markers.

[0077] (15) The apparatus 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.

[0078] (16) The apparatus according to (14) or (15), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in (f) to (j) below,

[0079] (f) A polynucleotide consisting of the base sequence shown in any of the sequence numbers 168 to 183, or a sequence of bases in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0080] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 168–183.

[0081] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 168-183 or the base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0082] (i) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequences 168–183 or a base sequence in which u is t, and

[0083] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.

[0084] (17) The device according to any one of (11) to (16), the device further comprising the ability to interact 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- Nucleic acids specifically bound to at least one of the following polynucleotides: 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.

[0085] (18) The apparatus 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-4688. -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-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-miR-4488, 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, and miR-6778-5p is hsa-miR-6778-5p.miR-557 is hsa-miR-557 and miR-6090 is hsa-miR-6090.

[0086] (19) The apparatus according to (17) or (18), wherein the nucleic acid is a polynucleotide selected from the polynucleotides shown in (k) to (o) below,

[0087] (k) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 184 to 224, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0088] (l) A polynucleotide containing the base sequence shown in any of the sequence numbers 184 to 224.

[0089] (m) A polynucleotide, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases, consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 184 to 224 or a base sequence in which u is t.

[0090] (n) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequence numbers 184–224 or a base sequence in which u is t, and

[0091] (o) is a polynucleotide that hybridizes with any of the polynucleotides (k) to (n) above under strict conditions.

[0092] (20) The apparatus according to any one of (11) to (19) is an apparatus for determination by hybridization technique.

[0093] (21) The apparatus according to (20), wherein the hybridization technique is a nucleic acid array technique.

[0094] (22) The device according to any one of (11) to (21) comprises at least two nucleic acids capable of specifically binding to at least two polynucleotides selected from all liver cancer markers described in (11) or (12).

[0095] (23) A method for detecting liver cancer, comprising: using a kit described in any one of (1) to (10) or an apparatus described in any one of (11) to (22), measuring the expression level of a target nucleic acid in a sample of a test subject, and using the measured expression level and the control expression level of a healthy body as measured in the same way to evaluate in vitro whether the test subject has liver cancer or not.

[0096] (24) The method according to (23) wherein the subject is a human.

[0097] (25) The method according to (23) or (24), wherein the above-mentioned specimen is blood, serum or plasma.

[0098] <Definitions of Terms>

[0099] The terms used in this specification have the following definitions.

[0100] The display of abbreviations such as nucleotide, polynucleotide, DNA, and RNA shall be in accordance with the “Guidelines for the Production of Instructions and Other Documents Containing Base Sequences or Amino Acid Sequences” (edited by the Japanese Patent Office) and common practice in this technical field.

[0101] In this specification, "polynucleotide" refers to nucleic acids comprising any of RNA, DNA, and RNA / DNA (chimeras). Furthermore, the aforementioned DNA includes any of cDNA, genomic DNA, and synthetic DNA. Additionally, the aforementioned RNA includes any 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 specified base sequences (which can be either native or non-native sequences), using, for example, an automated nucleic acid synthesizer. In this specification, "non-native sequence" is intended to be used in a broad sense, encompassing sequences that differ from native sequences, such as sequences containing one or more substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), etc. Furthermore, in this specification, polynucleotides and nucleic acids are used interchangeably.

[0102] In this specification, a “fragment” is a polynucleotide having a continuous portion of a polynucleotide sequence, preferably having a length of 15 or more bases, more preferably 17 or more bases, and more preferably 19 or more bases.

[0103] In this specification, the term "gene" is intended to include not only RNA and double-stranded DNA, but also the individual single-stranded DNA strands that constitute them, such as the positive (or sense) strand or the complementary (or antisense) strand. Furthermore, there is no particular limitation on its length.

[0104] Therefore, unless otherwise specified, the term "gene" in this specification includes: double-stranded DNA containing human genomic DNA, single-stranded DNA (positive strand) containing cDNA, single-stranded DNA (complementary strand) having a sequence complementary to the positive strand, microRNA (miRNA), fragments thereof, and transcripts thereof. Furthermore, "gene" is not only the "gene" indicated by a specific base sequence (or sequence number), but also a "nucleic acid" containing RNA with biological functions equivalent to the RNA encoded by that gene, such as mutants encoding homologs (i.e., orthologs), gene polymorphisms, and derivatives. Specifically, examples of such "nucleic acids" encoding homologs, mutants, or derivatives include those having a base sequence that hybridizes to the complementary sequence of any of the base sequences indicated by sequence numbers 1 to 765, or a base sequence in which u is t, under the strict conditions described below. Additionally, "gene" may include, without regard to differences in functional regions, for example, expression control regions, coding regions, exons, or introns. Furthermore, "genes" can be contained within cells, released outside cells and exist independently, or be enclosed in vesicles called exogenous bodies.

[0105] In this specification, "exosome" refers to a small vesicle surrounded by a lipid bilayer secreted by cells. Exosomes originate from multivesicular endosomes and, when released into the extracellular environment, sometimes contain biological substances such as RNA, DNA (genes), and proteins. Exosomes are known to be found in bodily fluids such as blood, serum, plasma, and lymph.

[0106] In this specification, "transcription product" refers to RNA synthesized using a gene's DNA sequence as a template. RNA polymerase binds to a site upstream of the gene called the promoter, synthesizing RNA in a manner complementary to the DNA's base sequence, causing a ribonucleotide to bind to the 3' end. This RNA contains not only the gene itself but also the complete sequence from the transcription start site to the end of the poly-A sequence, represented by expression control regions, coding regions, exons, or introns.

[0107] Furthermore, unless otherwise specified, “microRNA (miRNA)” in this specification is intended to be used as a 15-25 base non-coding RNA that is transcribed from a hairpin-like RNA precursor, cleaved by a dsRNA-cleaving enzyme with RNase III activity, encapsulated in a protein complex called RISC, and involved in the translational repression of mRNA. In addition, the term “miRNA” as used in this specification includes not only the “miRNA” indicated by the specific base sequence (or sequence number), but also its precursors (pre-miRNA, pri-miRNA), and miRNAs with equivalent biological functions, such as homologs (i.e., homologs or orthologs), mutants of gene 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 have a base sequence that hybridizes to the complementary sequence of any specific base sequence indicated by any of the sequence numbers 1-765 under the stringent conditions described below. In addition, the term “miRNA” used in this specification may refer to the gene product of a miR gene, which contains mature miRNA (e.g., a 15-25 base or 19-25 base noncoding RNA involved in the translation repression of mRNA as described above) or miRNA precursor (e.g., pre-miRNA or pri-miRNA as described above).

[0108] In this specification, "probe" includes polynucleotides and / or complementary polynucleotides used to specifically detect RNA or polynucleotides derived from gene expression.

[0109] In this specification, "primers" refers to polynucleotides and / or complementary polynucleotides that specifically recognize and amplify RNA produced through gene expression or polynucleotides derived from such RNA.

[0110] Here, complementary polynucleotides (complementary strands, negative strands) refer to polynucleotides whose full-length sequence or a portion thereof (here referred to as the positive strand for convenience) is complementary to the base pairing of a polynucleotide consisting of a base sequence defined by any of the sequence numbers 1 to 765, or a base sequence in that sequence where u is t, based on a base pairing such as A:T(U) or G:C. However, such complementary strands are not limited to the case where the base sequence of the target positive strand is completely complementary; they can also have a complementary relationship to the extent that they can hybridize with the target positive strand under strict conditions.

[0111] In this specification, "stringent conditions" refer to conditions under which the nucleic acid probe hybridizes to its target sequence to a greater extent (e.g., a value greater than the average background measurement plus the standard error of the background measurement multiplied by 2) compared 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 later.

[0112] In this specification, "Tm value" refers to the temperature at which the double-stranded portion of a polynucleotide denatures into a single strand, with the double strand and single strand existing in a 1:1 ratio.

[0113] In this specification, "mutant" in the case of nucleic acids refers to a naturally occurring mutant caused by polymorphism, mutation, etc., or a mutant containing one or more deletions, substitutions, additions, or insertions of one or more bases in any of the base sequences from sequence number 1 to 765, or in the base sequences where u is t, or in a portion thereof; or a mutant showing approximately 90%, approximately 95%, approximately 97%, approximately 98%, or approximately 99% identity with each of the base sequences or a portion thereof; or a nucleic acid that hybridizes with a polynucleotide or oligonucleotide containing the base sequence or a portion thereof under the strict conditions defined above.

[0114] In this specification, "multiple" refers to an integer of approximately 10, 9, 8, 7, 6, 5, 4, 3, or 2.

[0115] The mutants described in this manual can be created using known techniques such as site-directed mutagenesis and mutation introduction using PCR.

[0116] The "% identity" in this specification can be determined using the protein or gene search systems described above, with or without vacancies (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).

[0117] In this specification, "derivative" refers to modified nucleic acids, and not limited to, labeled derivatives such as fluorophores, derivatives containing modified nucleotides (e.g., nucleotides containing halogen, alkyl such as methyl, alkoxy such as methoxy, thio, carboxymethyl, etc., and nucleotides subjected to base reconstruction, double bond saturation, deamination, substitution of oxygen molecules for sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, PE et al., 1991, Science, Vol. 254, pp. 1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, pp. 5401-5404), etc.

[0118] The "nucleic acid" in this specification, capable of specifically binding to polynucleotides selected from the above-mentioned group of miRNAs used as biomarkers for liver cancer, is a synthetic or modulated nucleic acid. Specifically, it includes "nucleic acid probes" or "primers" and is used directly or indirectly to detect the presence of liver cancer in a test subject, or to diagnose the presence, severity, improvement, and sensitivity to liver cancer treatment, or to screen candidate substances useful for the prevention, improvement, or treatment of liver cancer. These include nucleotides, oligonucleotides, and polynucleotides that can specifically recognize and bind to the transcripts or cDNA synthesized from any of the sequences 1 to 765 in in vivo samples, particularly blood, urine, and other bodily fluids, associated with liver cancer. Based on the aforementioned properties, these nucleotides, oligonucleotides, and polynucleotides can be effectively used as probes for detecting the aforementioned genes expressed in vivo, in tissues, or in cells, and also as primers for amplifying the aforementioned genes expressed in vivo.

[0119] The term "test" as used in this manual may be replaced with terms such as examination, measurement, detection, or judgment support. Furthermore, the term "evaluation" in this manual is used to imply support for diagnosis or evaluation based on examination or measurement results.

[0120] The term "test subject" as used in this specification refers to mammals including humans, chimpanzees, pet animals such as dogs and cats, livestock such as cattle, horses, sheep, and goats, and rodents such as mice and rats. Furthermore, "healthy subject" refers to mammals that are not infected with the cancer being tested.

[0121] As used in this specification, "liver cancer" refers to "primary liver cancer" originating in the liver, including, for example, "hepatocellular carcinoma" and "mixed hepatocellular-cholangiocarcinoma" in which liver cells have become cancerous.

[0122] As used in this specification, "P" or "P-value" represents the probability, under the null hypothesis, of actually observing a statistic that is extreme compared to the statistic calculated from the data. Therefore, the smaller the "P" or "P-value," the more significant the difference is considered between the compared data.

[0123] In this instruction manual, "sensitivity" refers to the value of (number of true positives) / (number of true positives + number of false negatives). High sensitivity allows for early detection of liver cancer, leading to complete resection of the cancerous area and a reduced recurrence rate.

[0124] In this instruction manual, "specificity" refers to (number of true negatives) / (number of true negatives + number of false positives). High specificity prevents unnecessary additional testing due to misdiagnosing healthy individuals as liver cancer patients, thus reducing the burden on patients and lowering medical costs.

[0125] In this instruction manual, "accuracy" refers to the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy represents the proportion of correct judgments for all samples and serves as the primary indicator for evaluating test performance.

[0126] In this specification, the term "specimen" as the object of judgment, detection, or diagnosis refers to tissues and biological materials whose gene expression changes as liver cancer develops, progresses, and is effectively treated. Specifically, it refers to liver tissue and its surrounding blood vessels, lymph nodes, and organs; it also includes organs suspected of metastasis, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue extracts; serum and plasma modified from blood; and feces and hair. Further, it refers to biological samples extracted from these, specifically genes such as RNA and miRNA.

[0127] The terms "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" as used in this specification include the hsa-miR-1343-3p gene described in sequence number 1 (miRBase accession number MIMAT0019776), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-1343-3p", "hsa-mir-1343" (miRBase accession number MI0017320, sequence number 225) is known to form a hairpin-like structure.

[0128] The terms "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" as used in this specification include the hsa-miR-6726-5p gene described in sequence number 2 (miRBase accession number MIMAT0027353), homologs or orthologs of other species, etc. 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 to "hsa-miR-6726-5p", "hsa-mir-6726" (miRBase accession number MI0022571, sequence number 226), which forms a hairpin-like structure, is known.

[0129] The terms "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" as used in this specification include the hsa-miR-6515-3p gene described in sequence number 3 (miRBase accession number MIMAT0025487), homologs or orthologs of other species, etc. The hsa-miR-6515-3p gene can be obtained by the method described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. In addition, as a precursor of "hsa-miR-6515-3p", "hsa-mir-6515" (miRBase accession number MI0022227, sequence number 227) is known to form a hairpin-like structure.

[0130] The terms "hsa-miR-4651 gene" or "hsa-miR-4651" as used in this specification include the hsa-miR-4651 gene described in sequence number 4 (miRBase accession number MIMAT0019715), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4651", "hsa-mir-4651" (miRBase accession number MI0017279, sequence number 228) is known to form a hairpin-like structure.

[0131] The terms "hsa-miR-4257 gene" or "hsa-miR-4257" as used in this specification include the hsa-miR-4257 gene described in sequence number 5 (miRBase accession number MIMAT0016878), homologs or orthologs of other species, etc. 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 number MI0015856, sequence number 229) is known to form a hairpin-like structure.

[0132] The terms "hsa-miR-3188 gene" or "hsa-miR-3188" as used in this specification include the hsa-miR-3188 gene described in sequence number 6 (miRBase accession number MIMAT0015070), homologs or orthologs of other species, etc. The hsa-miR-3188 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-3188", "hsa-mir-3188" (miRBase accession number MI0014232, sequence number 230) is known to form a hairpin-like structure.

[0133] The terms "hsa-miR-6131 gene" or "hsa-miR-6131" as used in this specification include the hsa-miR-6131 gene described in sequence number 7 (miRBase accession number MIMAT0024615), homologs or orthologs of other species, etc. The hsa-miR-6131 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, Vol. 4, pp. 552-564. Furthermore, as a precursor to "hsa-miR-6131", "hsa-mir-6131" (miRBase accession number MI0021276, sequence number 231), which forms a hairpin-like structure, is known.

[0134] The terms "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" as used in this specification include the hsa-miR-6766-3p gene described in sequence number 8 (miRBase accession number MIMAT0027433), homologs or orthologs of other species, etc. 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 to "hsa-miR-6766-3p", the hairpin-like structure "hsa-mir-6766" (miRBase accession number MI0022611, sequence number 232) is known.

[0135] The terms "hsa-miR-7641 gene" or "hsa-miR-7641" as used in this specification include the hsa-miR-7641 gene described in sequence number 9 (miRBase accession number MIMAT0029782), homologs or orthologs of other species, etc. 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 to "hsa-miR-7641", "hsa-mir-7641-1" and "hsa-mir-7641-2" (miRBase accession numbers MI0024975, MI0024976, sequence numbers 233, 234) that form hairpin-like structures are known.

[0136] The terms "hsa-miR-1249 gene" or "hsa-miR-1249" as used in this specification include the hsa-miR-1249 gene described in sequence number 10 (miRBase accession number MIMAT0005901), homologs or orthologs of other species, etc. 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 number MI0006384, sequence number 235) is known to form a hairpin-like structure.

[0137] The terms "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" as used in this specification include the hsa-miR-3679-3p gene described in sequence number 11 (miRBase accession number MIMAT0018105), homologs or orthologs of other species, etc. The hsa-miR-3679-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, as a precursor of "hsa-miR-3679-3p", "hsa-mir-3679" (miRBase accession number MI0016080, sequence number 236) is known to form a hairpin-like structure.

[0138] The terms "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" as used in this specification include the hsa-miR-6787-5p gene described in sequence number 12 (miRBase accession number MIMAT0027474), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6787-5p", "hsa-mir-6787" (miRBase accession number MI0022632, sequence number 237) is known to form a hairpin-like structure.

[0139] The terms "hsa-miR-4454 gene" or "hsa-miR-4454" as used in this specification include the hsa-miR-4454 gene described in sequence number 13 (miRBase accession number MIMAT0018976), homologs or orthologs of other species, etc. The hsa-miR-4454 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4454", "hsa-mir-4454" (miRBase accession number MI0016800, sequence number 238) is known to form a hairpin-like structure.

[0140] The terms "hsa-miR-3135b gene" or "hsa-miR-3135b" as used in this specification include the hsa-miR-3135b gene described in sequence number 14 (miRBase accession number MIMAT0018985), homologs or orthologs of other species, etc. The hsa-miR-3135b 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-3135b", "hsa-mir-3135b" (miRBase accession number MI0016809, sequence number 239) that forms a hairpin-like structure is known.

[0141] The terms "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" as used in this specification include the hsa-miR-6765-3p gene described in sequence number 15 (miRBase accession number MIMAT0027431), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6765-3p", "hsa-mir-6765" (miRBase accession number MI0022610, sequence number 240) is known to form a hairpin-like structure.

[0142] The terms "hsa-miR-7975 gene" or "hsa-miR-7975" as used in this specification include the hsa-miR-7975 gene described in sequence number 16 (miRBase accession number MIMAT0031178), homologs or orthologs of other species, etc. The hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. In addition, as a precursor of "hsa-miR-7975", "hsa-mir-7975" (miRBase accession number MI0025751, sequence number 241) is known to form a hairpin-like structure.

[0143] The terms "hsa-miR-204-3p gene" or "hsa-miR-204-3p" as used in this specification include the hsa-miR-204-3p gene described in sequence number 17 (miRBase accession number MIMAT0022693), homologs or orthologs of other species, etc. The hsa-miR-204-3p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. In addition, as a precursor of "hsa-miR-204-3p", "hsa-mir-204" (miRBase accession number MI0000284, sequence number 242) is known to form a hairpin-like structure.

[0144] The terms "hsa-miR-7977 gene" or "hsa-miR-7977" as used in this specification include the hsa-miR-7977 gene described in sequence number 18 (miRBase accession number MIMAT0031180), homologs or orthologs of other species, etc. The hsa-miR-7977 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. In addition, as a precursor of "hsa-miR-7977", "hsa-mir-7977" (miRBase accession number MI0025753, sequence number 243) is known to form a hairpin-like structure.

[0145] The terms “hsa-miR-7110-5p gene” or “hsa-miR-7110-5p” as used in this specification include the hsa-miR-7110-5p gene described in sequence number 19 (miRBase accession number MIMAT0028117), homologs or orthologs of other species, etc. 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. In addition, as a precursor of “hsa-miR-7110-5p”, “hsa-mir-7110” (miRBase accession number MI0022961, sequence number 244) is known to form a hairpin-like structure.

[0146] The terms "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" as used in this specification include the hsa-miR-6717-5p gene described in sequence number 20 (miRBase accession number MIMAT0025846), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6717-5p", "hsa-mir-6717" (miRBase accession number MI0022551, sequence number 245) is known to form a hairpin-like structure.

[0147] The terms "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" as used in this specification include the hsa-miR-6870-5p gene described in sequence number 21 (miRBase accession number MIMAT0027640), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6870-5p", "hsa-mir-6870" (miRBase accession number MI0022717, sequence number 246) is known to form a hairpin-like structure.

[0148] The terms "hsa-miR-663b gene" or "hsa-miR-663b" as used in this specification include the hsa-miR-663b gene described in sequence number 22 (miRBase accession number MIMAT0005867), homologs or orthologs of other species, etc. 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 to "hsa-miR-663b", "hsa-mir-663b" (miRBase accession number MI0006336, sequence number 247) is known to form a hairpin-like structure.

[0149] The terms "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" as used in this specification include the hsa-miR-6875-5p gene described in sequence number 23 (miRBase accession number MIMAT0027650), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6875-5p", "hsa-mir-6875" (miRBase accession number MI0022722, sequence number 248) is known to form a hairpin-like structure.

[0150] The terms "hsa-miR-8072 gene" or "hsa-miR-8072" as used in this specification include the hsa-miR-8072 gene described in sequence number 24 (miRBase accession number MIMAT0030999), homologs or orthologs of other species, etc. The hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Furthermore, as a precursor to "hsa-miR-8072", "hsa-mir-8072" (miRBase accession number MI0025908, sequence number 249) is known to form a hairpin-like structure.

[0151] The terms “hsa-miR-6816-5p gene” or “hsa-miR-6816-5p” as used in this specification include the hsa-miR-6816-5p gene described in sequence number 25 (miRBase accession number MIMAT0027532), homologs or orthologs of other species, etc. 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. In addition, as a precursor of “hsa-miR-6816-5p”, “hsa-mir-6816” (miRBase accession number MI0022661, sequence number 250) is known to form a hairpin-like structure.

[0152] The terms "hsa-miR-4281 gene" or "hsa-miR-4281" as used in this specification include the hsa-miR-4281 gene described in sequence number 26 (miRBase accession number MIMAT0016907), homologs or orthologs of other species, etc. 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 number MI0015885, sequence number 251) is known to form a hairpin-like structure.

[0153] The terms "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" as used in this specification include the hsa-miR-6729-5p gene described in sequence number 27 (miRBase accession number MIMAT0027359), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6729-5p", "hsa-mir-6729" (miRBase accession number MI0022574, sequence number 252) is known to form a hairpin-like structure.

[0154] The terms "hsa-miR-8069 gene" or "hsa-miR-8069" as used in this specification include the hsa-miR-8069 gene described in sequence number 28 (miRBase accession number MIMAT0030996), homologs or orthologs of other species, etc. The hsa-miR-8069 gene can be obtained using the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Furthermore, as a precursor to "hsa-miR-8069", "hsa-mir-8069" (miRBase accession number MI0025905, sequence number 253) is known to form a hairpin-like structure.

[0155] The terms "hsa-miR-4706 gene" or "hsa-miR-4706" as used in this specification include the hsa-miR-4706 gene described in sequence number 29 (miRBase accession number MIMAT0019806), homologs or orthologs of other species, etc. The hsa-miR-4706 gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4706," the hairpin-like structure "hsa-mir-4706" (miRBase accession number MI0017339, sequence number 254) is known.

[0156] The terms "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" as used in this specification include the hsa-miR-7108-5p gene described in sequence number 30 (miRBase accession number MIMAT0028113), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-7108-5p", "hsa-mir-7108" (miRBase accession number MI0022959, sequence number 255) is known to form a hairpin-like structure.

[0157] The terms "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" as used in this specification include the hsa-miR-4433b-3p gene described in sequence number 31 (miRBase accession number MIMAT0030414), homologs or orthologs of other species, etc. The hsa-miR-4433b-3p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. In addition, as a precursor of "hsa-miR-4433b-3p", "hsa-mir-4433b" (miRBase accession number MI0025511, sequence number 256) is known to form a hairpin-like structure.

[0158] The terms "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" as used in this specification include the hsa-miR-6893-5p gene described in sequence number 32 (miRBase accession number MIMAT0027686), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6893-5p", "hsa-mir-6893" (miRBase accession number MI0022740, sequence number 257) is known to form a hairpin-like structure.

[0159] The terms "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" as used in this specification include the hsa-miR-6857-5p gene described in sequence number 33 (miRBase accession number MIMAT0027614), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6857-5p", "hsa-mir-6857" (miRBase accession number MI0022703, sequence number 258) is known to form a hairpin-like structure.

[0160] The terms "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" as used in this specification include the hsa-miR-1227-5p gene described in sequence number 34 (miRBase accession number MIMAT0022941), homologs or orthologs of other species, etc. The hsa-miR-1227-5p gene can be obtained using the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1227-5p", "hsa-mir-1227" (miRBase accession number MI0006316, sequence number 259), which forms a hairpin-like structure, is known.

[0161] The terms "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" as used in this specification include the hsa-miR-6741-5p gene described in sequence number 35 (miRBase accession number MIMAT0027383), homologs or orthologs of other species, etc. 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 to "hsa-miR-6741-5p", "hsa-mir-6741" (miRBase accession number MI0022586, sequence number 260), which forms a hairpin-like structure, is known.

[0162] The terms "hsa-miR-451a gene" or "hsa-miR-451a" as used in this specification include the hsa-miR-451a gene described in sequence number 36 (miRBase accession number MIMAT0001631), homologs or orthologs of other species, etc. 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 to "hsa-miR-451a", "hsa-mir-451a" (miRBase accession number MI0001729, sequence number 261) is known to form a hairpin-like structure.

[0163] The terms "hsa-miR-8063 gene" or "hsa-miR-8063" as used in this specification include the hsa-miR-8063 gene described in sequence number 37 (miRBase accession number MIMAT0030990), homologs or orthologs of other species, etc. The hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Furthermore, as a precursor to "hsa-miR-8063", "hsa-mir-8063" (miRBase accession number MI0025899, sequence number 262) is known to form a hairpin-like structure.

[0164] The terms "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" as used in this specification include the hsa-miR-3622a-5p gene described in sequence number 38 (miRBase accession number MIMAT0018003), homologs or orthologs of other species, etc. The hsa-miR-3622a-5p gene can be obtained by the method described in Witten D et al., 2010, BMCBiol, Vol. 8, p. 58. In addition, as a precursor of "hsa-miR-3622a-5p", "hsa-mir-3622a" (miRBase accession number MI0016013, sequence number 263) is known to form a hairpin-like structure.

[0165] The terms "hsa-miR-615-5p gene" or "hsa-miR-615-5p" as used in this specification include the hsa-miR-615-5p gene described in sequence number 39 (miRBase accession number MIMAT0004804), homologs or orthologs of other species, etc. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl AcadSci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor to "hsa-miR-615-5p", "hsa-mir-615" (miRBase accession number MI0003628, sequence number 264), which forms a hairpin-like structure, is known.

[0166] The terms "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" as used in this specification include the hsa-miR-128-1-5p gene described in sequence number 40 (miRBase accession number MIMAT0026477), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-128-1-5p", "hsa-mir-128-1" (miRBase accession number MI0000447, sequence number 265), which forms a hairpin-like structure, is known.

[0167] The terms "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" as used in this specification include the hsa-miR-6825-5p gene described in sequence number 41 (miRBase accession number MIMAT0027550), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6825-5p", "hsa-mir-6825" (miRBase accession number MI0022670, sequence number 266) is known to form a hairpin-like structure.

[0168] The terms "hsa-miR-1260b gene" or "hsa-miR-1260b" as used in this specification include the hsa-miR-1260b gene described in sequence number 42 (miRBase accession number MIMAT0015041), homologs or orthologs of other species, etc. 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 number MI0014197, sequence number 267) is known to form a hairpin-like structure.

[0169] The terms "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" as used in this specification include the hsa-miR-4433-3p gene described in sequence number 43 (miRBase accession number MIMAT0018949), homologs or orthologs of other species, etc. The hsa-miR-4433-3p 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-4433-3p", "hsa-mir-4433" (miRBase accession number MI0016773, sequence number 268) is known to form a hairpin-like structure.

[0170] The terms "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" as used in this specification include the hsa-miR-4665-5p gene described in sequence number 44 (miRBase accession number MIMAT0019739), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4665-5p", "hsa-mir-4665" (miRBase accession number MI0017295, sequence number 269) is known to form a hairpin-like structure.

[0171] The terms "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" as used in this specification include the hsa-miR-7845-5p gene described in sequence number 45 (miRBase accession number MIMAT0030420), homologs or orthologs of other species, etc. The hsa-miR-7845-5p gene can be obtained by the method described in Ple H et al., 2012, PLoS One, Vol. 7, e50746. In addition, as a precursor of "hsa-miR-7845-5p", "hsa-mir-7845" (miRBase accession number MI0025515, sequence number 270) is known to form a hairpin-like structure.

[0172] The terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" as used in this specification include the hsa-miR-1908-5p gene described in sequence number 46 (miRBase accession number MIMAT0007881), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-1908-5p", "hsa-mir-1908" (miRBase accession number MI0008329, sequence number 271), which forms a hairpin-like structure, is known.

[0173] The terms "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" as used in this specification include the hsa-miR-6840-3p gene described in sequence number 47 (miRBase accession number MIMAT0027583), homologs or orthologs of other species, etc. 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 to "hsa-miR-6840-3p", "hsa-mir-6840" (miRBase accession number MI0022686, sequence number 272), which forms a hairpin-like structure, is known.

[0174] The terms "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" as used in this specification include the hsa-miR-6765-5p gene described in sequence number 48 (miRBase accession number MIMAT0027430), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6765-5p", "hsa-mir-6765" (miRBase accession number MI0022610, sequence number 240) is known to form a hairpin-like structure.

[0175] The terms "hsa-miR-296-5p gene" or "hsa-miR-296-5p" as used in this specification include the hsa-miR-296-5p gene described in sequence number 49 (miRBase accession number MIMAT0000690), homologs or orthologs of other species, etc. The hsa-miR-296-5p gene can be obtained by the method described in Houbavy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. In addition, as a precursor of "hsa-miR-296-5p", "hsa-mir-296" (miRBase accession number MI0000747, sequence number 273) is known to form a hairpin-like structure.

[0176] The terms "hsa-miR-3675-3p gene" or "hsa-miR-3675-3p" as used in this specification include the hsa-miR-3675-3p gene described in sequence number 50 (miRBase accession number MIMAT0018099), homologs or orthologs of other species, etc. The hsa-miR-3675-3p gene can be obtained by the method described in Vaz C et al., 2010, BMC Genomics, Vol. 11, p. 288. In addition, as a precursor of "hsa-miR-3675-3p", "hsa-mir-3675" (miRBase accession number MI0016076, sequence number 274) is known to form a hairpin-like structure.

[0177] The terms "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" as used in this specification include the hsa-miR-6781-5p gene described in sequence number 51 (miRBase accession number MIMAT0027462), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6781-5p", "hsa-mir-6781" (miRBase accession number MI0022626, sequence number 275) is known to form a hairpin-like structure.

[0178] The terms "hsa-miR-423-5p gene" or "hsa-miR-423-5p" as used in this specification include the hsa-miR-423-5p gene described in sequence number 52 (miRBase accession number MIMAT0004748), homologs or orthologs of other organisms, etc. 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 number MI0001445, sequence number 276) is known to form a hairpin-like structure.

[0179] The terms "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" as used in this specification include the hsa-miR-3663-3p gene described in sequence number 53 (miRBase accession number MIMAT0018085), homologs or orthologs of other species, etc. The hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. In addition, as a precursor of "hsa-miR-3663-3p", "hsa-mir-3663" (miRBase accession number MI0016064, sequence number 277) is known to form a hairpin-like structure.

[0180] The terms "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" as used in this specification include the hsa-miR-6784-5p gene described in sequence number 54 (miRBase accession number MIMAT0027468), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6784-5p", "hsa-mir-6784" (miRBase accession number MI0022629, sequence number 278) is known to form a hairpin-like structure.

[0181] The terms "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" as used in this specification include the hsa-miR-6749-5p gene described in sequence number 55 (miRBase accession number MIMAT0027398), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6749-5p", "hsa-mir-6749" (miRBase accession number MI0022594, sequence number 279) is known to form a hairpin-like structure.

[0182] The terms "hsa-miR-1231 gene" or "hsa-miR-1231" as used in this specification include the hsa-miR-1231 gene described in sequence number 56 (miRBase accession number MIMAT0005586), homologs or orthologs of other species, etc. The hsa-miR-1231 gene can be obtained using the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1231," the hairpin-like structure "hsa-mir-1231" (miRBase accession number MI0006321, sequence number 280) is known.

[0183] The terms "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" as used in this specification include the hsa-miR-4746-3p gene described in sequence number 57 (miRBase accession number MIMAT0019881), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4746-3p", "hsa-mir-4746" (miRBase accession number MI0017385, sequence number 281) is known to form a hairpin-like structure.

[0184] The terms "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" as used in this specification include the hsa-miR-6780b-5p gene described in sequence number 58 (miRBase accession number MIMAT0027572), homologs or orthologs of other species, etc. The hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6780b-5p", the hairpin-like structure "hsa-mir-6780b" (miRBase accession number MI0022681, sequence number 282) is known.

[0185] The terms "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" as used in this specification include the hsa-miR-4758-5p gene described in sequence number 59 (miRBase accession number MIMAT0019903), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4758-5p", "hsa-mir-4758" (miRBase accession number MI0017399, sequence number 283) is known to form a hairpin-like structure.

[0186] The terms "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" as used in this specification include the hsa-miR-3679-5p gene described in sequence number 60 (miRBase accession number MIMAT0018104), homologs or orthologs of other species, etc. The hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, as a precursor of "hsa-miR-3679-5p", "hsa-mir-3679" (miRBase accession number MI0016080, sequence number 236) is known to form a hairpin-like structure.

[0187] The terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" as used in this specification include the hsa-miR-3184-5p gene described in sequence number 61 (miRBase accession number MIMAT0015064), homologs or orthologs of other species, etc. The hsa-miR-3184-5p 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-3184-5p", "hsa-mir-3184" (miRBase accession number MI0014226, sequence number 284) is known to form a hairpin-like structure.

[0188] The terms "hsa-miR-6125 gene" or "hsa-miR-6125" as used in this specification include the hsa-miR-6125 gene described in sequence number 62 (miRBase accession number MIMAT0024598), homologs or orthologs of other species, etc. 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 to "hsa-miR-6125", "hsa-mir-6125" (miRBase accession number MI0021259, sequence number 285) is known to form a hairpin-like structure.

[0189] The terms "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" as used in this specification include the hsa-miR-6721-5p gene described in sequence number 63 (miRBase accession number MIMAT0025852), homologs or orthologs of other species, etc. 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 to "hsa-miR-6721-5p", "hsa-mir-6721" (miRBase accession number MI0022556, sequence number 286), which forms a hairpin-like structure, is known.

[0190] The terms "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" as used in this specification include the hsa-miR-6791-5p gene described in sequence number 64 (miRBase accession number MIMAT0027482), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6791-5p", "hsa-mir-6791" (miRBase accession number MI0022636, sequence number 287) is known to form a hairpin-like structure.

[0191] As used in this specification, the terms "hsa-miR-3185 gene" or "hsa-miR-3185" include the hsa-miR-3185 gene described in sequence number 65 (miRBase accession number MIMAT0015065), homologs or orthologs of other species, etc. The hsa-miR-3185 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-3185", "hsa-mir-3185" (miRBase accession number MI0014227, sequence number 288) is known to form a hairpin-like structure.

[0192] The terms "hsa-miR-1260a gene" or "hsa-miR-1260a" as used in this specification include the hsa-miR-1260a gene described in sequence number 66 (miRBase accession number MIMAT0005911), homologs or orthologs of other species, etc. 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 number MI0006394, sequence number 289) is known to form a hairpin-like structure.

[0193] The terms "hsa-miR-3197 gene" or "hsa-miR-3197" as used in this specification include the hsa-miR-3197 gene described in sequence number 67 (miRBase accession number MIMAT0015082), homologs or orthologs of other species, etc. The hsa-miR-3197 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-3197", "hsa-mir-3197" (miRBase accession number MI0014245, sequence number 290) is known to form a hairpin-like structure.

[0194] The terms "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" as used in this specification include the hsa-miR-6845-5p gene described in sequence number 68 (miRBase accession number MIMAT0027590), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6845-5p", "hsa-mir-6845" (miRBase accession number MI0022691, sequence number 291) is known to form a hairpin-like structure.

[0195] The terms "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" as used in this specification include the hsa-miR-6887-5p gene described in sequence number 69 (miRBase accession number MIMAT0027674), homologs or orthologs of other species, etc. 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 to "hsa-miR-6887-5p", "hsa-mir-6887" (miRBase accession number MI0022734, sequence number 292), which forms a hairpin-like structure, is known.

[0196] The terms "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" as used in this specification include the hsa-miR-6738-5p gene described in sequence number 70 (miRBase accession number MIMAT0027377), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6738-5p", "hsa-mir-6738" (miRBase accession number MI0022583, sequence number 293) is known to form a hairpin-like structure.

[0197] The terms "hsa-miR-6872-3p gene" or "hsa-miR-6872-3p" as used in this specification include the hsa-miR-6872-3p gene described in sequence number 71 (miRBase accession number MIMAT0027645), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6872-3p", "hsa-mir-6872" (miRBase accession number MI0022719, sequence number 294) is known to form a hairpin-like structure.

[0198] As used in this specification, the terms "hsa-miR-4497 gene" or "hsa-miR-4497" include the hsa-miR-4497 gene described in sequence number 72 (miRBase accession number MIMAT0019032), homologs or orthologs of other species, etc. 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 number MI0016859, sequence number 295) is known to form a hairpin-like structure.

[0199] The terms "hsa-miR-1229-5p gene" or "hsa-miR-1229-5p" as used in this specification include the hsa-miR-1229-5p gene described in sequence number 73 (miRBase accession number MIMAT0022942), homologs or orthologs of other species, etc. The hsa-miR-1229-5p gene can be obtained using the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1229-5p", "hsa-mir-1229" (miRBase accession number MI0006319, sequence number 296), which forms a hairpin-like structure, is known.

[0200] The terms "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" as used in this specification include the hsa-miR-6820-5p gene described in sequence number 74 (miRBase accession number MIMAT0027540), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6820-5p", "hsa-mir-6820" (miRBase accession number MI0022665, sequence number 297) is known to form a hairpin-like structure.

[0201] The terms "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" as used in this specification include the hsa-miR-6777-5p gene described in sequence number 75 (miRBase accession number MIMAT0027454), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6777-5p", "hsa-mir-6777" (miRBase accession number MI0022622, sequence number 298), which forms a hairpin-like structure, is known.

[0202] The terms "hsa-miR-3917 gene" or "hsa-miR-3917" as used in this specification include the hsa-miR-3917 gene described in sequence number 76 (miRBase accession number MIMAT0018191), homologs or orthologs of other species, etc. The hsa-miR-3917 gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, Vol. 5, e9637. In addition, as a precursor of "hsa-miR-3917", "hsa-mir-3917" (miRBase accession number MI0016423, sequence number 299) is known to form a hairpin-like structure.

[0203] The terms "hsa-miR-5787 gene" or "hsa-miR-5787" as used in this specification include the hsa-miR-5787 gene described in sequence number 77 (miRBase accession number MIMAT0023252), homologs or orthologs of other species, etc. 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 to "hsa-miR-5787", "hsa-mir-5787" (miRBase accession number MI0019797, sequence number 300) is known to form a hairpin-like structure.

[0204] The terms "hsa-miR-4286 gene" or "hsa-miR-4286" as used in this specification include the hsa-miR-4286 gene described in sequence number 78 (miRBase accession number MIMAT0016916), homologs or orthologs of other species, etc. 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 number MI0015894, sequence number 301) is known to form a hairpin-like structure.

[0205] The terms "hsa-miR-6877-5p gene" or "hsa-miR-6877-5p" as used in this specification include the hsa-miR-6877-5p gene described in sequence number 79 (miRBase accession number MIMAT0027654), homologs or orthologs of other species, etc. 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 to "hsa-miR-6877-5p", "hsa-mir-6877" (miRBase accession number MI0022724, sequence number 302), which forms a hairpin-like structure, is known.

[0206] The terms "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" as used in this specification include the hsa-miR-1225-3p gene described in sequence number 80 (miRBase accession number MIMAT0005573), homologs or orthologs of other species, etc. The hsa-miR-1225-3p gene can be obtained using the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1225-3p", "hsa-mir-1225" (miRBase accession number MI0006311, sequence number 303), which forms a hairpin-like structure, is known.

[0207] The terms "hsa-miR-6088 gene" or "hsa-miR-6088" as used in this specification include the hsa-miR-6088 gene described in sequence number 81 (miRBase accession number MIMAT0023713), homologs or orthologs of other species, etc. The hsa-miR-6088 gene can be obtained using the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor to "hsa-miR-6088," "hsa-mir-6088" (miRBase accession number MI0020365, sequence number 304), which forms a hairpin-like structure, is known.

[0208] The terms "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" as used in this specification include the hsa-miR-6800-5p gene described in sequence number 82 (miRBase accession number MIMAT0027500), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6800-5p", "hsa-mir-6800" (miRBase accession number MI0022645, sequence number 305) is known to form a hairpin-like structure.

[0209] The terms "hsa-miR-1246 gene" or "hsa-miR-1246" as used in this specification include the hsa-miR-1246 gene described in sequence number 83 (miRBase accession number MIMAT0005898), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-1246", "hsa-mir-1246" (miRBase accession number MI0006381, sequence number 306), which forms a hairpin-like structure, is known.

[0210] The terms "hsa-miR-4467 gene" or "hsa-miR-4467" as used in this specification include the hsa-miR-4467 gene described in sequence number 84 (miRBase accession number MIMAT0018994), homologs or orthologs of other species, etc. 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 number MI0016818, sequence number 307) is known to form a hairpin-like structure.

[0211] The terms "hsa-miR-4419b gene" or "hsa-miR-4419b" as used in this specification include the hsa-miR-4419b gene described in sequence number 85 (miRBase accession number MIMAT0019034), homologs or orthologs of other species, etc. The hsa-miR-4419b 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-4419b", "hsa-mir-4419b" (miRBase accession number MI0016861, sequence number 308) is known to form a hairpin-like structure.

[0212] The terms "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" as used in this specification include the hsa-miR-1914-3p gene described in sequence number 86 (miRBase accession number MIMAT0007890), homologs or orthologs of other species, etc. 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 to "hsa-miR-1914-3p", "hsa-mir-1914" (miRBase accession number MI0008335, sequence number 309), which forms a hairpin-like structure, is known.

[0213] The terms "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" as used in this specification include the hsa-miR-4632-5p gene described in sequence number 87 (miRBase accession number MIMAT0022977), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4632-5p", "hsa-mir-4632" (miRBase accession number MI0017259, sequence number 310), which forms a hairpin-like structure, is known.

[0214] The terms "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" as used in this specification include the hsa-miR-1915-5p gene described in sequence number 88 (miRBase accession number MIMAT0007891), homologs or orthologs of other species, etc. 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 to "hsa-miR-1915-5p", "hsa-mir-1915" (miRBase accession number MI0008336, sequence number 311), which forms a hairpin-like structure, is known.

[0215] The terms "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" as used in this specification include the hsa-miR-3940-5p gene described in sequence number 89 (miRBase accession number MIMAT0019229), homologs or orthologs of other species, etc. The hsa-miR-3940-5p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. In addition, as a precursor of "hsa-miR-3940-5p", "hsa-mir-3940" (miRBase accession number MI0016597, sequence number 312) is known to form a hairpin-like structure.

[0216] The terms "hsa-miR-1185-2-3p gene" or "hsa-miR-1185-2-3p" as used in this specification include the hsa-miR-1185-2-3p gene described in sequence number 90 (miRBase accession number MIMAT0022713), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-1185-2-3p", "hsa-mir-1185-2" (miRBase accession number MI0003821, sequence number 313) forming a hairpin-like structure is known.

[0217] The terms "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" as used in this specification include the hsa-miR-6746-5p gene described in sequence number 91 (miRBase accession number MIMAT0027392), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-6746-5p", "hsa-mir-6746" (miRBase accession number MI0022591, sequence number 314) is known to form a hairpin-like structure.

[0218] The terms "hsa-miR-5001-5p gene" or "hsa-miR-5001-5p" as used in this specification include the hsa-miR-5001-5p gene described in sequence number 92 (miRBase accession number MIMAT0021021), homologs or orthologs of other organisms, etc. 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. In addition, as a precursor of "hsa-miR-5001-5p", "hsa-mir-5001" (miRBase accession number MI0017867, sequence number 315) is known to form a hairpin-like structure.

[0219] The terms "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" as used in this specification include the hsa-miR-1228-5p gene described in sequence number 93 (miRBase accession number MIMAT0005582), homologs or orthologs of other species, etc. The hsa-miR-1228-5p gene can be obtained using the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1228-5p", "hsa-mir-1228" (miRBase accession number MI0006318, sequence number 316), which forms a hairpin-like structure, is known.

[0220] The terms "hsa-miR-5572 gene" or "hsa-miR-5572" as used in this specification include the hsa-miR-5572 gene described in sequence number 94 (miRBase accession number MIMAT0022260), homologs or orthologs of other species, etc. 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 number MI0019117, sequence number 317) is known to form a hairpin-like structure.

[0221] The terms "hsa-miR-4327 gene" or "hsa-miR-4327" as used in this specification include the hsa-miR-4327 gene described in sequence number 95 (miRBase accession number MIMAT0016889), homologs or orthologs of other species, etc. 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 number MI0015867, sequence number 318) is known to form a hairpin-like structure.

[0222] The terms "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" as used in this specification include the hsa-miR-4638-5p gene described in sequence number 96 (miRBase accession number MIMAT0019695), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4638-5p", "hsa-mir-4638" (miRBase accession number MI0017265, sequence number 319) is known to form a hairpin-like structure.

[0223] The terms "hsa-miR-6799-5p gene" or "hsa-miR-6799-5p" as used in this specification include the hsa-miR-6799-5p gene described in sequence number 97 (miRBase accession number MIMAT0027498), homologs or orthologs of other species, etc. 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 to "hsa-miR-6799-5p", "hsa-mir-6799" (miRBase accession number MI0022644, sequence number 320), which forms a hairpin-like structure, is known.

[0224] The terms "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" as used in this specification include the hsa-miR-6861-5p gene described in sequence number 98 (miRBase accession number MIMAT0027623), homologs or orthologs of other species, etc. 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 to "hsa-miR-6861-5p", "hsa-mir-6861" (miRBase accession number MI0022708, sequence number 321), which forms a hairpin-like structure, is known.

[0225] The terms "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" as used in this specification include the hsa-miR-6727-5p gene described in sequence number 99 (miRBase accession number MIMAT0027355), homologs or orthologs of other species, etc. 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 to "hsa-miR-6727-5p", "hsa-mir-6727" (miRBase accession number MI0022572, sequence number 322), which forms a hairpin-like structure, is known.

[0226] The terms "hsa-miR-4513 gene" or "hsa-miR-4513" as used in this specification include the hsa-miR-4513 gene described in sequence number 100 (miRBase accession number MIMAT0019050), homologs or orthologs of other species, etc. The hsa-miR-4513 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-4513", "hsa-mir-4513" (miRBase accession number MI0016879, sequence number 323) is known to form a hairpin-like structure.

[0227] The terms "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" as used in this specification include the hsa-miR-6805-3p gene described in sequence number 101 (miRBase accession number MIMAT0027511), homologs or orthologs of other species, etc. The hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6805-3p", "hsa-mir-6805" (miRBase accession number MI0022650, sequence number 324), which forms a hairpin-like structure, is known.

[0228] The terms "hsa-miR-6808-5p gene" or "hsa-miR-6808-5p" as used in this specification include the hsa-miR-6808-5p gene described in sequence number 102 (miRBase accession number MIMAT0027516), homologs or orthologs of other species, etc. The hsa-miR-6808-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6808-5p", "hsa-mir-6808" (miRBase accession number MI0022653, sequence number 325), which forms a hairpin-like structure, is known.

[0229] The terms "hsa-miR-4449 gene" or "hsa-miR-4449" as used in this specification include the hsa-miR-4449 gene described in sequence number 103 (miRBase accession number MIMAT0018968), homologs or orthologs of other species, etc. 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 number MI0016792, sequence number 326) is known to form a hairpin-like structure.

[0230] The terms "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" as used in this specification include the hsa-miR-1199-5p gene described in sequence number 104 (miRBase accession number MIMAT0031119), homologs or orthologs of other species, etc. 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 to "hsa-miR-1199-5p", "hsa-mir-1199" (miRBase accession number MI0020340, sequence number 327), which forms a hairpin-like structure, is known.

[0231] The terms "hsa-miR-1275 gene" or "hsa-miR-1275" as used in this specification include the hsa-miR-1275 gene described in sequence number 105 (miRBase accession number MIMAT0005929), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-1275", "hsa-mir-1275" (miRBase accession number MI0006415, sequence number 328) is known to form a hairpin-like structure.

[0232] The terms "hsa-miR-4792 gene" or "hsa-miR-4792" as used in this specification include the hsa-miR-4792 gene described in sequence number 106 (miRBase accession number MIMAT0019964), homologs or orthologs of other species, etc. The hsa-miR-4792 gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4792", "hsa-mir-4792" (miRBase accession number MI0017439, sequence number 329) is known to form a hairpin-like structure.

[0233] The terms "hsa-miR-4443 gene" or "hsa-miR-4443" as used in this specification include the hsa-miR-4443 gene described in sequence number 107 (miRBase accession number MIMAT0018961), homologs or orthologs of other species, etc. The hsa-miR-4443 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-4443", "hsa-mir-4443" (miRBase accession number MI0016786, sequence number 330) is known to form a hairpin-like structure.

[0234] The terms "hsa-miR-6891-5p gene" or "hsa-miR-6891-5p" as used in this specification include the hsa-miR-6891-5p gene described in sequence number 108 (miRBase accession number MIMAT0027682), homologs or orthologs of other species, etc. The hsa-miR-6891-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. In addition, as a precursor of "hsa-miR-6891-5p", "hsa-mir-6891" (miRBase accession number MI0022738, sequence number 331) is known to form a hairpin-like structure.

[0235] The terms "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" as used in this specification include the hsa-miR-6826-5p gene described in sequence number 109 (miRBase accession number MIMAT0027552), homologs or orthologs of other species, etc. The hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6826-5p", "hsa-mir-6826" (miRBase accession number MI0022671, sequence number 332), which forms a hairpin-like structure, is known.

[0236] The terms "hsa-miR-6807-5p gene" or "hsa-miR-6807-5p" as used in this specification include the hsa-miR-6807-5p gene described in sequence number 110 (miRBase accession number MIMAT0027514), homologs or orthologs of other species, etc. The hsa-miR-6807-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6807-5p", "hsa-mir-6807" (miRBase accession number MI0022652, sequence number 333), which forms a hairpin-like structure, is known.

[0237] The terms "hsa-miR-7150 gene" or "hsa-miR-7150" as used in this specification include the hsa-miR-7150 gene described in sequence number 111 (miRBase accession number MIMAT0028211), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-7150", "hsa-mir-7150" (miRBase accession number MI0023610, sequence number 334) is known to form a hairpin-like structure.

[0238] The terms "hsa-miR-4534 gene" or "hsa-miR-4534" as used in this specification include the hsa-miR-4534 gene described in sequence number 112 (miRBase accession number MIMAT0019073), homologs or orthologs of other species, etc. The hsa-miR-4534 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-4534", "hsa-mir-4534" (miRBase accession number MI0016901, sequence number 335) is known to form a hairpin-like structure.

[0239] The terms "hsa-miR-4476 gene" or "hsa-miR-4476" as used in this specification include the hsa-miR-4476 gene described in sequence number 113 (miRBase accession number MIMAT0019003), homologs or orthologs of other species, etc. 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 number MI0016828, sequence number 336) is known to form a hairpin-like structure.

[0240] The terms "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" as used in this specification include the hsa-miR-4649-5p gene described in sequence number 114 (miRBase accession number MIMAT0019711), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4649-5p", "hsa-mir-4649" (miRBase accession number MI0017276, sequence number 337) is known to form a hairpin-like structure.

[0241] The terms "hsa-miR-4525 gene" or "hsa-miR-4525" as used in this specification include the hsa-miR-4525 gene described in sequence number 115 (miRBase accession number MIMAT0019064), homologs or orthologs of other species, etc. The hsa-miR-4525 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-4525", "hsa-mir-4525" (miRBase accession number MI0016892, sequence number 338) is known to form a hairpin-like structure.

[0242] The terms "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" as used in this specification include the hsa-miR-1915-3p gene described in sequence number 116 (miRBase accession number MIMAT0007892), homologs or orthologs of other species, etc. 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 to "hsa-miR-1915-3p", "hsa-mir-1915" (miRBase accession number MI0008336, sequence number 311), which forms a hairpin-like structure, is known.

[0243] The terms "hsa-miR-4516 gene" or "hsa-miR-4516" as used in this specification include the hsa-miR-4516 gene described in sequence number 117 (miRBase accession number MIMAT0019053), homologs or orthologs of other species, etc. The hsa-miR-4516 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-4516", "hsa-mir-4516" (miRBase accession number MI0016882, sequence number 339) is known to form a hairpin-like structure.

[0244] The terms "hsa-miR-4417 gene" or "hsa-miR-4417" as used in this specification include the hsa-miR-4417 gene described in sequence number 118 (miRBase accession number MIMAT0018929), homologs or orthologs of other species, etc. The hsa-miR-4417 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-4417", "hsa-mir-4417" (miRBase accession number MI0016753, sequence number 340) is known to form a hairpin-like structure.

[0245] The terms "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" as used in this specification include the hsa-miR-642b-3p gene described in sequence number 119 (miRBase accession number MIMAT0018444), homologs or orthologs of other species, etc. The hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. In addition, as a precursor of "hsa-miR-642b-3p", "hsa-mir-642b" (miRBase accession number MI0016685, sequence number 341) is known to form a hairpin-like structure.

[0246] The terms "hsa-miR-3141 gene" or "hsa-miR-3141" as used in this specification include the hsa-miR-3141 gene described in sequence number 120 (miRBase accession number MIMAT0015010), homologs or orthologs of other species, etc. The hsa-miR-3141 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-3141", "hsa-mir-3141" (miRBase accession number MI0014165, sequence number 342) is known to form a hairpin-like structure.

[0247] The terms "hsa-miR-5100 gene" or "hsa-miR-5100" as used in this specification include the hsa-miR-5100 gene described in sequence number 121 (miRBase accession number MIMAT0022259), homologs or orthologs of other species, etc. 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 number MI0019116, sequence number 343) is known to form a hairpin-like structure.

[0248] The terms "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" as used in this specification include the hsa-miR-6848-5p gene described in sequence number 122 (miRBase accession number MIMAT0027596), homologs or orthologs of other species, etc. The hsa-miR-6848-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6848-5p", "hsa-mir-6848" (miRBase accession number MI0022694, sequence number 344), which forms a hairpin-like structure, is known.

[0249] The terms "hsa-miR-4739 gene" or "hsa-miR-4739" as used in this specification include the hsa-miR-4739 gene described in sequence number 123 (miRBase accession number MIMAT0019868), homologs or orthologs of other species, etc. 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 number MI0017377, sequence number 345) is known to form a hairpin-like structure.

[0250] The terms "hsa-miR-4459 gene" or "hsa-miR-4459" as used in this specification include the hsa-miR-4459 gene described in sequence number 124 (miRBase accession number MIMAT0018981), homologs or orthologs of other species, etc. 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 to "hsa-miR-4459", "hsa-mir-4459" (miRBase accession number MI0016805, sequence number 346) is known to form a hairpin-like structure.

[0251] The terms "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" as used in this specification include the hsa-miR-1237-5p gene described in sequence number 125 (miRBase accession number MIMAT0022946), homologs or orthologs of other species, etc. The hsa-miR-1237-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1237-5p", "hsa-mir-1237" (miRBase accession number MI0006327, sequence number 347), which forms a hairpin-like structure, is known.

[0252] The terms "hsa-miR-296-3p gene" or "hsa-miR-296-3p" as used in this specification include the hsa-miR-296-3p gene described in sequence number 126 (miRBase accession number MIMAT0004679), homologs or orthologs of other species, etc. The hsa-miR-296-3p gene can be obtained using the method described in Houbavy HB et al., 2003, Dev Cell, Vol. 5, pp. 351-358. Furthermore, as a precursor to "hsa-miR-296-3p", "hsa-mir-296" (miRBase accession number MI0000747, sequence number 273), which forms a hairpin-like structure, is known.

[0253] The terms "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" as used in this specification include the hsa-miR-4665-3p gene described in sequence number 127 (miRBase accession number MIMAT0019740), homologs or orthologs of other species, etc. The hsa-miR-4665-3p gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4665-3p", "hsa-mir-4665" (miRBase accession number MI0017295, sequence number 269), which forms a hairpin-like structure, is known.

[0254] The terms "hsa-miR-6786-5p gene" or "hsa-miR-6786-5p" as used in this specification include the hsa-miR-6786-5p gene described in sequence number 128 (miRBase accession number MIMAT0027472), homologs or orthologs of other species, etc. The hsa-miR-6786-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6786-5p", "hsa-mir-6786" (miRBase accession number MI0022631, sequence number 348), which forms a hairpin-like structure, is known.

[0255] The terms "hsa-miR-4258 gene" or "hsa-miR-4258" as used in this specification include the hsa-miR-4258 gene described in sequence number 129 (miRBase accession number MIMAT0016879), homologs or orthologs of other species, etc. The hsa-miR-4258 gene can be obtained using the method described in Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Furthermore, as a precursor to "hsa-miR-4258," the hairpin-like structure "hsa-mir-4258" (miRBase accession number MI0015857, sequence number 349) is known.

[0256] The terms "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" as used in this specification include the hsa-miR-6510-5p gene described in sequence number 130 (miRBase accession number MIMAT0025476), homologs or orthologs of other species, etc. The hsa-miR-6510-5p gene can be obtained by the method described in Joyce CE et al., 2011, Hum MolGenet, Vol. 20, pp. 4025-4040. In addition, as a precursor of "hsa-miR-6510-5p", "hsa-mir-6510" (miRBase accession number MI0022222, sequence number 350) is known to form a hairpin-like structure.

[0257] The terms "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" as used in this specification include the hsa-miR-1343-5p gene described in sequence number 131 (miRBase accession number MIMAT0027038), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-1343-5p", "hsa-mir-1343" (miRBase accession number MI0017320, sequence number 225) is known to form a hairpin-like structure.

[0258] The terms "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" as used in this specification include the hsa-miR-1247-3p gene described in sequence number 132 (miRBase accession number MIMAT0022721), homologs or orthologs of other species, etc. 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 number MI0006382, sequence number 351) is known to form a hairpin-like structure.

[0259] The terms "hsa-miR-6805-5p gene" or "hsa-miR-6805-5p" as used in this specification include the hsa-miR-6805-5p gene described in sequence number 133 (miRBase accession number MIMAT0027510), homologs or orthologs of other species, etc. The hsa-miR-6805-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6805-5p", "hsa-mir-6805" (miRBase accession number MI0022650, sequence number 324), which forms a hairpin-like structure, is known.

[0260] The terms "hsa-miR-4492 gene" or "hsa-miR-4492" as used in this specification include the hsa-miR-4492 gene described in sequence number 134 (miRBase accession number MIMAT0019027), homologs or orthologs of other species, etc. The hsa-miR-4492 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Furthermore, as a precursor to "hsa-miR-4492", "hsa-mir-4492" (miRBase accession number MI0016854, sequence number 352) is known to form a hairpin-like structure.

[0261] The terms "hsa-miR-1469 gene" or "hsa-miR-1469" as used in this specification include the hsa-miR-1469 gene described in sequence number 135 (miRBase accession number MIMAT0007347), homologs or orthologs of other species, etc. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. In addition, as a precursor of "hsa-miR-1469", "hsa-mir-1469" (miRBase accession number MI0007074, sequence number 353) that forms a hairpin-like structure is known.

[0262] The terms "hsa-miR-1268b gene" or "hsa-miR-1268b" as used in this specification include the hsa-miR-1268b gene described in sequence number 136 (miRBase accession number MIMAT0018925), homologs or orthologs of other species, etc. The hsa-miR-1268b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. In addition, as a precursor of "hsa-miR-1268b", "hsa-mir-1268b" (miRBase accession number MI0016748, sequence number 354) is known to form a hairpin-like structure.

[0263] The terms "hsa-miR-6858-5p gene" or "hsa-miR-6858-5p" as used in this specification include the hsa-miR-6858-5p gene described in sequence number 137 (miRBase accession number MIMAT0027616), homologs or orthologs of other species, etc. The hsa-miR-6858-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6858-5p", "hsa-mir-6858" (miRBase accession number MI0022704, sequence number 355), which forms a hairpin-like structure, is known.

[0264] The terms "hsa-miR-3937 gene" or "hsa-miR-3937" as used in this specification include the hsa-miR-3937 gene described in sequence number 138 (miRBase accession number MIMAT0018352), homologs or orthologs of other species, etc. The hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, Vol. 5, e10563. In addition, as a precursor of "hsa-miR-3937", "hsa-mir-3937" (miRBase accession number MI0016593, sequence number 356) is known to form a hairpin-like structure.

[0265] The terms "hsa-miR-939-5p gene" or "hsa-miR-939-5p" as used in this specification include the hsa-miR-939-5p gene described in sequence number 139 (miRBase accession number MIMAT0004982), homologs or orthologs of other species, etc. 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 to "hsa-miR-939-5p", "hsa-mir-939" (miRBase accession number MI0005761, sequence number 357), which forms a hairpin-like structure, is known.

[0266] The terms "hsa-miR-3656 gene" or "hsa-miR-3656" as used in this specification include the hsa-miR-3656 gene described in sequence number 140 (miRBase accession number MIMAT0018076), homologs or orthologs of other species, etc. 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 to "hsa-miR-3656," the hairpin-like structure "hsa-mir-3656" (miRBase accession number MI0016056, sequence number 358) is known.

[0267] The terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" as used in this specification include the hsa-miR-744-5p gene described in sequence number 141 (miRBase accession number MIMAT0004945), homologs or orthologs of other species, etc. 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 to "hsa-miR-744-5p", "hsa-mir-744" (miRBase accession number MI0005559, sequence number 359), which forms a hairpin-like structure, is known.

[0268] The terms "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" as used in this specification include the hsa-miR-4687-3p gene described in sequence number 142 (miRBase accession number MIMAT0019775), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4687-3p", "hsa-mir-4687" (miRBase accession number MI0017319, sequence number 360) is known to form a hairpin-like structure.

[0269] The terms "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" as used in this specification include the hsa-miR-4763-3p gene described in sequence number 143 (miRBase accession number MIMAT0019913), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4763-3p", "hsa-mir-4763" (miRBase accession number MI0017404, sequence number 361) is known to form a hairpin-like structure.

[0270] The terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" as used in this specification include the hsa-miR-3620-5p gene described in sequence number 144 (miRBase accession number MIMAT0022967), homologs or orthologs of other species, etc. The hsa-miR-3620-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. In addition, as a precursor of "hsa-miR-3620-5p", "hsa-mir-3620" (miRBase accession number MI0016011, sequence number 362) is known to form a hairpin-like structure.

[0271] The terms "hsa-miR-3195 gene" or "hsa-miR-3195" as used in this specification include the hsa-miR-3195 gene described in sequence number 145 (miRBase accession number MIMAT0015079), homologs or orthologs of other species, etc. The hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, Vol. 5, e9685. In addition, as a precursor of "hsa-miR-3195", "hsa-mir-3195" (miRBase accession number MI0014240, sequence number 363) that forms a hairpin-like structure is known.

[0272] The terms "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" as used in this specification include the hsa-miR-6842-5p gene described in sequence number 146 (miRBase accession number MIMAT0027586), homologs or orthologs of other species, etc. The hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6842-5p", "hsa-mir-6842" (miRBase accession number MI0022688, sequence number 364), which forms a hairpin-like structure, is known.

[0273] The terms "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" as used in this specification include the hsa-miR-4707-5p gene described in sequence number 147 (miRBase accession number MIMAT0019807), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4707-5p", "hsa-mir-4707" (miRBase accession number MI0017340, sequence number 365) is known to form a hairpin-like structure.

[0274] The terms "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" as used in this specification include the hsa-miR-642a-3p gene described in sequence number 148 (miRBase accession number MIMAT0020924), homologs or orthologs of other species, etc. 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 to "hsa-miR-642a-3p", "hsa-mir-642a" (miRBase accession number MI0003657, sequence number 366), which forms a hairpin-like structure, is known.

[0275] The terms "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" as used in this specification include the hsa-miR-7113-3p gene described in sequence number 149 (miRBase accession number MIMAT0028124), homologs or orthologs of other species, etc. The hsa-miR-7113-3p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. In addition, as a precursor of "hsa-miR-7113-3p", "hsa-mir-7113" (miRBase accession number MI0022964, sequence number 367) is known to form a hairpin-like structure.

[0276] The terms "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" as used in this specification include the hsa-miR-4728-5p gene described in sequence number 150 (miRBase accession number MIMAT0019849), homologs or orthologs of other species, etc. 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 to "hsa-miR-4728-5p", "hsa-mir-4728" (miRBase accession number MI0017365, sequence number 368), which forms a hairpin-like structure, is known.

[0277] The terms "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" as used in this specification include the hsa-miR-5195-3p gene described in sequence number 151 (miRBase accession number MIMAT0021127), homologs or orthologs of other species, etc. 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 to "hsa-miR-5195-3p", "hsa-mir-5195" (miRBase accession number MI0018174, sequence number 369), which forms a hairpin-like structure, is known.

[0278] The terms "hsa-miR-1185-1-3p gene" or "hsa-miR-1185-1-3p" as used in this specification include the hsa-miR-1185-1-3p gene described in sequence number 152 (miRBase accession number MIMAT0022838), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-1185-1-3p", "hsa-mir-1185-1" (miRBase accession number MI0003844, sequence number 370) is known to form a hairpin-like structure.

[0279] The terms "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" as used in this specification include the hsa-miR-6774-5p gene described in sequence number 153 (miRBase accession number MIMAT0027448), homologs or orthologs of other species, etc. The hsa-miR-6774-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6774-5p", "hsa-mir-6774" (miRBase accession number MI0022619, sequence number 371), which forms a hairpin-like structure, is known.

[0280] The terms "hsa-miR-8059 gene" or "hsa-miR-8059" as used in this specification include the hsa-miR-8059 gene described in sequence number 154 (miRBase accession number MIMAT0030986), homologs or orthologs of other species, etc. The hsa-miR-8059 gene can be obtained using the method described in Wang HJ et al., 2013, Shock, Vol. 39, pp. 480-487. Furthermore, as a precursor to "hsa-miR-8059", "hsa-mir-8059" (miRBase accession number MI0025895, sequence number 372) is known to form a hairpin-like structure.

[0281] As used in this specification, the terms "hsa-miR-3131 gene" or "hsa-miR-3131" include the hsa-miR-3131 gene described in sequence number 155 (miRBase accession number MIMAT0014996), homologs or orthologs of other species, etc. The hsa-miR-3131 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-3131", "hsa-mir-3131" (miRBase accession number MI0014151, sequence number 373) is known to form a hairpin-like structure.

[0282] The terms "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" as used in this specification include the hsa-miR-7847-3p gene described in sequence number 156 (miRBase accession number MIMAT0030422), homologs or orthologs of other species, etc. 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 to "hsa-miR-7847-3p", "hsa-mir-7847" (miRBase accession number MI0025517, sequence number 374), which forms a hairpin-like structure, is known.

[0283] The terms "hsa-miR-4463 gene" or "hsa-miR-4463" as used in this specification include the hsa-miR-4463 gene described in sequence number 157 (miRBase accession number MIMAT0018987), homologs or orthologs of other species, etc. 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 number MI0016811, sequence number 375) is known to form a hairpin-like structure.

[0284] The terms "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" as used in this specification include the hsa-miR-128-2-5p gene described in sequence number 158 (miRBase accession number MIMAT0031095), homologs or orthologs of other species, etc. 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 to "hsa-miR-128-2-5p", "hsa-mir-128-2" (miRBase accession number MI0000727, sequence number 376), which forms a hairpin-like structure, is known.

[0285] The terms "hsa-miR-4508 gene" or "hsa-miR-4508" as used in this specification include the hsa-miR-4508 gene described in sequence number 159 (miRBase accession number MIMAT0019045), homologs or orthologs of other species, etc. The hsa-miR-4508 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-4508", "hsa-mir-4508" (miRBase accession number MI0016872, sequence number 377) is known to form a hairpin-like structure.

[0286] The terms "hsa-miR-6806-5p gene" or "hsa-miR-6806-5p" as used in this specification include the hsa-miR-6806-5p gene described in sequence number 160 (miRBase accession number MIMAT0027512), homologs or orthologs of other species, etc. The hsa-miR-6806-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. In addition, as a precursor of "hsa-miR-6806-5p", "hsa-mir-6806" (miRBase accession number MI0022651, sequence number 378) is known to form a hairpin-like structure.

[0287] The terms "hsa-miR-7111-5p gene" or "hsa-miR-7111-5p" as used in this specification include the hsa-miR-7111-5p gene described in sequence number 161 (miRBase accession number MIMAT0028119), homologs or orthologs of other species, etc. The hsa-miR-7111-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. In addition, as a precursor of "hsa-miR-7111-5p", "hsa-mir-7111" (miRBase accession number MI0022962, sequence number 379), which forms a hairpin-like structure, is known.

[0288] The terms "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" as used in this specification include the hsa-miR-6782-5p gene described in sequence number 162 (miRBase accession number MIMAT0027464), homologs or orthologs of other species, etc. The hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6782-5p", "hsa-mir-6782" (miRBase accession number MI0022627, sequence number 380), which forms a hairpin-like structure, is known.

[0289] The terms "hsa-miR-4734 gene" or "hsa-miR-4734" as used in this specification include the hsa-miR-4734 gene described in sequence number 163 (miRBase accession number MIMAT0019859), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4734", "hsa-mir-4734" (miRBase accession number MI0017371, sequence number 381) is known to form a hairpin-like structure.

[0290] The terms "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" as used in this specification include the hsa-miR-3162-5p gene described in sequence number 164 (miRBase accession number MIMAT0015036), homologs or orthologs of other species, etc. The hsa-miR-3162-5p 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-3162-5p", "hsa-mir-3162" (miRBase accession number MI0014192, sequence number 382) is known to form a hairpin-like structure.

[0291] The terms "hsa-miR-887-3p gene" or "hsa-miR-887-3p" as used in this specification include the hsa-miR-887-3p gene described in sequence number 165 (miRBase accession number MIMAT0004951), homologs or orthologs of other species, etc. 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 to "hsa-miR-887-3p", "hsa-mir-887" (miRBase accession number MI0005562, sequence number 383), which forms a hairpin-like structure, is known.

[0292] The terms "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" as used in this specification include the hsa-miR-6752-5p gene described in sequence number 166 (miRBase accession number MIMAT0027404), homologs or orthologs of other species, etc. The hsa-miR-6752-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6752-5p", "hsa-mir-6752" (miRBase accession number MI0022597, sequence number 384), which forms a hairpin-like structure, is known.

[0293] The terms "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" as used in this specification include the hsa-miR-6724-5p gene described in sequence number 167 (miRBase accession number MIMAT0025856), homologs or orthologs of other species, etc. 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 to "hsa-miR-6724-5p", "hsa-mir-6724" (miRBase accession number MI0022559, sequence number 385), which forms a hairpin-like structure, is known.

[0294] The terms "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" as used in this specification include the hsa-miR-23b-3p gene described in sequence number 168 (miRBase accession number MIMAT0000418), homologs or orthologs of other species, etc. The hsa-miR-23b-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. In addition, as a precursor of "hsa-miR-23b-3p", "hsa-mir-23b" (miRBase accession number MI0000439, sequence number 386) is known to form a hairpin-like structure.

[0295] The terms "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" as used in this specification include the hsa-miR-23a-3p gene described in sequence number 169 (miRBase accession number MIMAT0000078), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-23a-3p", "hsa-mir-23a" (miRBase accession number MI0000079, sequence number 387) is known to form a hairpin-like structure.

[0296] The terms "hsa-miR-625-3p gene" or "hsa-miR-625-3p" as used in this specification include the hsa-miR-625-3p gene described in sequence number 170 (miRBase accession number MIMAT0004808), homologs or orthologs of other species, etc. The hsa-miR-625-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl AcadSci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor to "hsa-miR-625-3p", "hsa-mir-625" (miRBase accession number MI0003639, sequence number 388), which forms a hairpin-like structure, is known.

[0297] The terms "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" as used in this specification include the hsa-miR-1228-3p gene described in sequence number 171 (miRBase accession number MIMAT0005583), homologs or orthologs of other organisms, etc. The hsa-miR-1228-3p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1228-3p", "hsa-mir-1228" (miRBase accession number MI0006318, sequence number 316), which forms a hairpin-like structure, is known.

[0298] The terms "hsa-miR-614 gene" or "hsa-miR-614" as used in this specification include the hsa-miR-614 gene described in sequence number 172 (miRBase accession number MIMAT0003282), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-614," "hsa-mir-614" (miRBase accession number MI0003627, sequence number 389), which forms a hairpin-like structure, is known.

[0299] The terms "hsa-miR-1913 gene" or "hsa-miR-1913" as used in this specification include the hsa-miR-1913 gene described in sequence number 173 (miRBase accession number MIMAT0007888), homologs or orthologs of other species, etc. The hsa-miR-1913 gene can be obtained using the method described in Bar M et al., 2008, Stem Cells, Vol. 26, pp. 2496-2505. Furthermore, as a precursor to "hsa-miR-1913," "hsa-mir-1913" (miRBase accession number MI0008334, sequence number 390), which forms a hairpin-like structure, is known.

[0300] The terms "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" as used in this specification include the hsa-miR-92a-2-5p gene described in sequence number 174 (miRBase accession number MIMAT0004508), homologs or orthologs of other species, etc. 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 to "hsa-miR-92a-2-5p", "hsa-mir-92a-2" (miRBase accession number MI0000094, sequence number 391), which forms a hairpin-like structure, is known.

[0301] The terms "hsa-miR-187-5p gene" or "hsa-miR-187-5p" as used in this specification include the hsa-miR-187-5p gene described in sequence number 175 (miRBase accession number MIMAT0004561), homologs or orthologs of other species, etc. The hsa-miR-187-5p gene can be obtained by the method described in Lim LP et al., 2003, Science, Vol. 299, p1540. In addition, as a precursor of "hsa-miR-187-5p", "hsa-mir-187" (miRBase accession number MI0000274, sequence number 392) is known to form a hairpin-like structure.

[0302] The terms "hsa-miR-16-5p gene" or "hsa-miR-16-5p" as used in this specification include the hsa-miR-16-5p gene described in sequence number 176 (miRBase accession number MIMAT0000069), homologs or orthologs of other species, etc. 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. In addition, as precursors to "hsa-miR-16-5p", "hsa-mir-16-1" and "hsa-mir-16-2" (miRBase accession numbers MI0000070, MI0000115, sequence numbers 393, 394) are known to form hairpin-like structures.

[0303] The terms "hsa-miR-92b-3p gene" or "hsa-miR-92b-3p" as used in this specification include the hsa-miR-92b-3p gene described in sequence number 177 (miRBase accession number MIMAT0003218), homologs or orthologs of other species, etc. The hsa-miR-92b-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl AcadSci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor to "hsa-miR-92b-3p", "hsa-mir-92b" (miRBase accession number MI0003560, sequence number 395), which forms a hairpin-like structure, is known.

[0304] The terms "hsa-miR-150-3p gene" or "hsa-miR-150-3p" as used in this specification include the hsa-miR-150-3p gene described in sequence number 178 (miRBase accession number MIMAT0004610), homologs or orthologs of other species, etc. The hsa-miR-150-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, CurrBiol, Vol. 12, pp. 735-739. In addition, as a precursor of "hsa-miR-150-3p", "hsa-mir-150" (miRBase accession number MI0000479, sequence number 396) is known to form a hairpin-like structure.

[0305] The terms "hsa-miR-564 gene" or "hsa-miR-564" as used in this specification include the hsa-miR-564 gene described in sequence number 179 (miRBase accession number MIMAT0003228), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-564," "hsa-mir-564" (miRBase accession number MI0003570, sequence number 397), which forms a hairpin-like structure, is known.

[0306] The terms "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" as used in this specification include the hsa-miR-125a-3p gene described in sequence number 180 (miRBase accession number MIMAT0004602), homologs or orthologs of other species, etc. 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 to "hsa-miR-125a-3p", "hsa-mir-125a" (miRBase accession number MI0000469, sequence number 398), which forms a hairpin-like structure, is known.

[0307] The terms "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" as used in this specification include the hsa-miR-92b-5p gene described in sequence number 181 (miRBase accession number MIMAT0004792), homologs or orthologs of other species, etc. The hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl AcadSci USA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor to "hsa-miR-92b-5p", "hsa-mir-92b" (miRBase accession number MI0003560, sequence number 395), which forms a hairpin-like structure, is known.

[0308] The terms "hsa-miR-92a-3p gene" or "hsa-miR-92a-3p" as used in this specification include the hsa-miR-92a-3p gene described in sequence number 182 (miRBase accession number MIMAT0000092), homologs or orthologs of other species, etc. 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. In addition, as precursors to "hsa-miR-92a-3p", "hsa-mir-92a-1" and "hsa-mir-92a-2" (miRBase accession numbers MI0000093, MI0000094, sequence numbers 399, 391) are known to form hairpin-like structures.

[0309] The terms "hsa-miR-663a gene" or "hsa-miR-663a" as used in this specification include the hsa-miR-663a gene described in sequence number 183 (miRBase accession number MIMAT0003326), homologs or orthologs of other species, etc. The hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U SA, Vol. 103, pp. 3687-3692. Furthermore, as a precursor to "hsa-miR-663a", "hsa-mir-663a" (miRBase accession number MI0003672, sequence number 400), which forms a hairpin-like structure, is known.

[0310] The terms "hsa-miR-4688 gene" or "hsa-miR-4688" as used in this specification include the hsa-miR-4688 gene described in sequence number 184 (miRBase accession number MIMAT0019777), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4688", "hsa-mir-4688" (miRBase accession number MI0017321, sequence number 401) is known to form a hairpin-like structure.

[0311] The terms "hsa-miR-4648 gene" or "hsa-miR-4648" as used in this specification include the hsa-miR-4648 gene described in sequence number 185 (miRBase accession number MIMAT0019710), homologs or orthologs of other species, etc. The hsa-miR-4648 gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4648", "hsa-mir-4648" (miRBase accession number MI0017275, sequence number 402) is known to form a hairpin-like structure.

[0312] The terms "hsa-miR-6085 gene" or "hsa-miR-6085" as used in this specification include the hsa-miR-6085 gene described in sequence number 186 (miRBase accession number MIMAT0023710), homologs or orthologs of other organisms, etc. The hsa-miR-6085 gene can be obtained using the method described in Voellenkle C et al., 2012, RNA, Vol. 18, pp. 472-484. Furthermore, as a precursor to "hsa-miR-6085," "hsa-mir-6085" (miRBase accession number MI0020362, sequence number 403), which forms a hairpin-like structure, is known.

[0313] The terms "hsa-miR-6126 gene" or "hsa-miR-6126" as used in this specification include the hsa-miR-6126 gene described in sequence number 187 (miRBase accession number MIMAT0024599), homologs or orthologs of other species, etc. 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 to "hsa-miR-6126", "hsa-mir-6126" (miRBase accession number MI0021260, sequence number 404) is known to form a hairpin-like structure.

[0314] The terms "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" as used in this specification include the hsa-miR-6880-5p gene described in sequence number 188 (miRBase accession number MIMAT0027660), homologs or orthologs of other species, etc. The hsa-miR-6880-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6880-5p", "hsa-mir-6880" (miRBase accession number MI0022727, sequence number 405), which forms a hairpin-like structure, is known.

[0315] The terms "hsa-miR-328-5p gene" or "hsa-miR-328-5p" as used in this specification include the hsa-miR-328-5p gene described in sequence number 189 (miRBase accession number MIMAT0026486), homologs or orthologs of other organisms, etc. 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 to "hsa-miR-328-5p", "hsa-mir-328" (miRBase accession number MI0000804, sequence number 406), which forms a hairpin-like structure, is known.

[0316] The terms "hsa-miR-6768-5p gene" or "hsa-miR-6768-5p" as used in this specification include the hsa-miR-6768-5p gene described in sequence number 190 (miRBase accession number MIMAT0027436), homologs or orthologs of other species, etc. The hsa-miR-6768-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6768-5p", "hsa-mir-6768" (miRBase accession number MI0022613, sequence number 407), which forms a hairpin-like structure, is known.

[0317] The terms "hsa-miR-3180 gene" or "hsa-miR-3180" as used in this specification include the hsa-miR-3180 gene described in sequence number 191 (miRBase accession number MIMAT0018178), homologs or orthologs of other species, etc. 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 to "hsa-miR-3180", "hsa-mir-3180-4" and "hsa-mir-3180-5" (miRBase accession numbers MI0016408, MI0016409, sequence numbers 408, 409) that form hairpin-like structures are known.

[0318] The terms "hsa-miR-6087 gene" or "hsa-miR-6087" as used in this specification include the hsa-miR-6087 gene described in sequence number 192 (miRBase accession number MIMAT0023712), homologs or orthologs of other organisms, etc. The hsa-miR-6087 gene can be obtained using the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor to "hsa-miR-6087", "hsa-mir-6087" (miRBase accession number MI0020364, sequence number 410) is known to form a hairpin-like structure.

[0319] The terms "hsa-miR-1273g-3p gene" or "hsa-miR-1273g-3p" as used in this specification include the hsa-miR-1273g-3p gene described in sequence number 193 (miRBase accession number MIMAT0022742), homologs or orthologs of other species, etc. The hsa-miR-1273g-3p gene can be obtained by the method described in Reshmi G et al., 2011, Genomics, Vol. 97, pp. 333-340. Furthermore, as a precursor to "hsa-miR-1273g-3p", "hsa-mir-1273g" (miRBase accession number MI0018003, sequence number 411), which forms a hairpin-like structure, is known.

[0320] The terms "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" as used in this specification include the hsa-miR-1225-5p gene described in sequence number 194 (miRBase accession number MIMAT0005572), homologs or orthologs of other organisms, etc. The hsa-miR-1225-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1225-5p", "hsa-mir-1225" (miRBase accession number MI0006311, sequence number 303), which forms a hairpin-like structure, is known.

[0321] The terms "hsa-miR-3196 gene" or "hsa-miR-3196" as used in this specification include the hsa-miR-3196 gene described in sequence number 195 (miRBase accession number MIMAT0015080), homologs or orthologs of other species, etc. The hsa-miR-3196 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-3196", "hsa-mir-3196" (miRBase accession number MI0014241, sequence number 412) is known to form a hairpin-like structure.

[0322] The terms "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" as used in this specification include the hsa-miR-4695-5p gene described in sequence number 196 (miRBase accession number MIMAT0019788), homologs or orthologs of other species, etc. The hsa-miR-4695-5p gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4695-5p", "hsa-mir-4695" (miRBase accession number MI0017328, sequence number 413), which forms a hairpin-like structure, is known.

[0323] The terms "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" as used in this specification include the hsa-miR-6732-5p gene described in sequence number 197 (miRBase accession number MIMAT0027365), homologs or orthologs of other species, etc. The hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6732-5p", "hsa-mir-6732" (miRBase accession number MI0022577, sequence number 414), which forms a hairpin-like structure, is known.

[0324] The terms "hsa-miR-638 gene" or "hsa-miR-638" as used in this specification include the hsa-miR-638 gene described in sequence number 198 (miRBase accession number MIMAT0003308), homologs or orthologs of other species, etc. 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 to "hsa-miR-638," "hsa-mir-638" (miRBase accession number MI0003653, sequence number 415), which forms a hairpin-like structure, is known.

[0325] The terms "hsa-miR-6813-5p gene" or "hsa-miR-6813-5p" as used in this specification include the hsa-miR-6813-5p gene described in sequence number 199 (miRBase accession number MIMAT0027526), ​​homologs or orthologs of other species, etc. The hsa-miR-6813-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. In addition, as a precursor of "hsa-miR-6813-5p", "hsa-mir-6813" (miRBase accession number MI0022658, sequence number 416) is known to form a hairpin-like structure.

[0326] The terms "hsa-miR-665 gene" or "hsa-miR-665" as used in this specification include the hsa-miR-665 gene described in sequence number 200 (miRBase accession number MIMAT0004952), homologs or orthologs of other species, etc. 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 to "hsa-miR-665", "hsa-mir-665" (miRBase accession number MI0005563, sequence number 417) is known to form a hairpin-like structure.

[0327] The terms "hsa-miR-486-3p gene" or "hsa-miR-486-3p" as used in this specification include the hsa-miR-486-3p gene described in sequence number 201 (miRBase accession number MIMAT0004762), homologs or orthologs of other species, etc. 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. In addition, as precursors to "hsa-miR-486-3p", "hsa-mir-486" and "hsa-mir-486-2" (miRBase accession numbers MI0002470, MI0023622, sequence numbers 418, 419) that form hairpin-like structures are known.

[0328] The terms "hsa-miR-4466 gene" or "hsa-miR-4466" as used in this specification include the hsa-miR-4466 gene described in sequence number 202 (miRBase accession number MIMAT0018993), homologs or orthologs of other species, etc. 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 number MI0016817, sequence number 420) is known to form a hairpin-like structure.

[0329] The terms "hsa-miR-30c-1-3p gene" or "hsa-miR-30c-1-3p" as used in this specification include the hsa-miR-30c-1-3p gene described in sequence number 203 (miRBase accession number MIMAT0004674), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-30c-1-3p", "hsa-mir-30c-1" (miRBase accession number MI0000736, sequence number 421), which forms a hairpin-like structure, is known.

[0330] The terms "hsa-miR-3621 gene" or "hsa-miR-3621" as used in this specification include the hsa-miR-3621 gene described in sequence number 204 (miRBase accession number MIMAT0018002), homologs or orthologs of other species, etc. The hsa-miR-3621 gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. In addition, as a precursor of "hsa-miR-3621", "hsa-mir-3621" (miRBase accession number MI0016012, sequence number 422) is known to form a hairpin-like structure.

[0331] The terms "hsa-miR-6743-5p gene" or "hsa-miR-6743-5p" as used in this specification include the hsa-miR-6743-5p gene described in sequence number 205 (miRBase accession number MIMAT0027387), homologs or orthologs of other species, etc. The hsa-miR-6743-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6743-5p", "hsa-mir-6743" (miRBase accession number MI0022588, sequence number 423), which forms a hairpin-like structure, is known.

[0332] The terms "hsa-miR-4298 gene" or "hsa-miR-4298" as used in this specification include the hsa-miR-4298 gene described in sequence number 206 (miRBase accession number MIMAT0016852), homologs or orthologs of other species, etc. 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 number MI0015830, sequence number 424) is known to form a hairpin-like structure.

[0333] The terms "hsa-miR-4741 gene" or "hsa-miR-4741" as used in this specification include the hsa-miR-4741 gene described in sequence number 207 (miRBase accession number MIMAT0019871), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4741", "hsa-mir-4741" (miRBase accession number MI0017379, sequence number 425) is known to form a hairpin-like structure.

[0334] The terms "hsa-miR-3619-3p gene" or "hsa-miR-3619-3p" as used in this specification include the hsa-miR-3619-3p gene described in sequence number 208 (miRBase accession number MIMAT0019219), homologs or orthologs of other species, etc. The hsa-miR-3619-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, Vol. 8, p58. In addition, as a precursor of "hsa-miR-3619-3p", "hsa-mir-3619" (miRBase accession number MI0016009, sequence number 426) is known to form a hairpin-like structure.

[0335] The terms "hsa-miR-6824-5p gene" or "hsa-miR-6824-5p" as used in this specification include the hsa-miR-6824-5p gene described in sequence number 209 (miRBase accession number MIMAT0027548), homologs or orthologs of other species, etc. The hsa-miR-6824-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6824-5p", "hsa-mir-6824" (miRBase accession number MI0022669, sequence number 427), which forms a hairpin-like structure, is known.

[0336] The terms "hsa-miR-5698 gene" or "hsa-miR-5698" as used in this specification include the hsa-miR-5698 gene described in sequence number 210 (miRBase accession number MIMAT0022491), homologs or orthologs of other species, etc. 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 number MI0019305, sequence number 428) that forms a hairpin-like structure is known.

[0337] The terms "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" as used in this specification include the hsa-miR-371a-5p gene described in sequence number 211 (miRBase accession number MIMAT0004687), homologs or orthologs of other species, etc. 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 to "hsa-miR-371a-5p", "hsa-mir-371a" (miRBase accession number MI0000779, sequence number 429), which forms a hairpin-like structure, is known.

[0338] The terms "hsa-miR-4488 gene" or "hsa-miR-4488" as used in this specification include the hsa-miR-4488 gene described in sequence number 212 (miRBase accession number MIMAT0019022), homologs or orthologs of other species, etc. The hsa-miR-4488 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-4488", "hsa-mir-4488" (miRBase accession number MI0016849, sequence number 430) is known to form a hairpin-like structure.

[0339] The terms "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" as used in this specification include the hsa-miR-1233-5p gene described in sequence number 213 (miRBase accession number MIMAT0022943), homologs or orthologs of other species, etc. The hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. In addition, as precursors to "hsa-miR-1233-5p", "hsa-mir-1233-1" and "hsa-mir-1233-2" (miRBase accession numbers MI0006323, MI0015973, sequence numbers 431, 432) that form hairpin-like structures are known.

[0340] The terms "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" as used in this specification include the hsa-miR-4723-5p gene described in sequence number 214 (miRBase accession number MIMAT0019838), homologs or orthologs of other species, etc. 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 to "hsa-miR-4723-5p", "hsa-mir-4723" (miRBase accession number MI0017359, sequence number 433), which forms a hairpin-like structure, is known.

[0341] The terms "hsa-miR-24-3p gene" or "hsa-miR-24-3p" as used in this specification include the hsa-miR-24-3p gene described in sequence number 215 (miRBase accession number MIMAT0000080), homologs or orthologs of other species, etc. 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 to "hsa-miR-24-3p", "hsa-mir-24-1" and "hsa-mir-24-2" (miRBase accession numbers MI0000080, MI0000081, sequence numbers 434, 435) are known to form hairpin-like structures.

[0342] The terms "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" as used in this specification include the hsa-miR-1238-5p gene described in sequence number 216 (miRBase accession number MIMAT0022947), homologs or orthologs of other species, etc. The hsa-miR-1238-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, Vol. 28, pp. 328-336. Furthermore, as a precursor to "hsa-miR-1238-5p", "hsa-mir-1238" (miRBase accession number MI0006328, sequence number 436), which forms a hairpin-like structure, is known.

[0343] The terms "hsa-miR-4442 gene" or "hsa-miR-4442" as used in this specification include the hsa-miR-4442 gene described in sequence number 217 (miRBase accession number MIMAT0018960), homologs or orthologs of other species, etc. 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 number MI0016785, sequence number 437) is known to form a hairpin-like structure.

[0344] The terms "hsa-miR-3928-3p gene" or "hsa-miR-3928-3p" as used in this specification include the hsa-miR-3928-3p gene described in sequence number 218 (miRBase accession number MIMAT0018205), homologs or orthologs of other species, etc. The hsa-miR-3928-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoSOne, Vol. 5, e9637. In addition, as a precursor of "hsa-miR-3928-3p", "hsa-mir-3928" (miRBase accession number MI0016438, sequence number 438) is known to form a hairpin-like structure.

[0345] The terms "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" as used in this specification include the hsa-miR-6716-5p gene described in sequence number 219 (miRBase accession number MIMAT0025844), homologs or orthologs of other species, etc. 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 to "hsa-miR-6716-5p", "hsa-mir-6716" (miRBase accession number MI0022550, sequence number 439), which forms a hairpin-like structure, is known.

[0346] The terms "hsa-miR-6089 gene" or "hsa-miR-6089" as used in this specification include the hsa-miR-6089 gene described in sequence number 220 (miRBase accession number MIMAT0023714), homologs or orthologs of other species, etc. 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 to "hsa-miR-6089", "hsa-mir-6089-1" and "hsa-mir-6089-2" (miRBase accession numbers MI0020366, MI0023563, sequence numbers 440, 441) are known to form hairpin-like structures.

[0347] The terms "hsa-miR-6124 gene" or "hsa-miR-6124" as used in this specification include the hsa-miR-6124 gene described in sequence number 221 (miRBase accession number MIMAT0024597), homologs or orthologs of other species, etc. 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 to "hsa-miR-6124", "hsa-mir-6124" (miRBase accession number MI0021258, sequence number 442) is known to form a hairpin-like structure.

[0348] The terms "hsa-miR-6778-5p gene" or "hsa-miR-6778-5p" as used in this specification include the hsa-miR-6778-5p gene described in sequence number 222 (miRBase accession number MIMAT0027456), homologs or orthologs of other species, etc. The hsa-miR-6778-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6778-5p", "hsa-mir-6778" (miRBase accession number MI0022623, sequence number 443), which forms a hairpin-like structure, is known.

[0349] The terms "hsa-miR-557 gene" or "hsa-miR-557" as used in this specification include the hsa-miR-557 gene described in sequence number 223 (miRBase accession number MIMAT0003221), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-557", "hsa-mir-557" (miRBase accession number MI0003563, sequence number 444) is known to form a hairpin-like structure.

[0350] The terms "hsa-miR-6090 gene" or "hsa-miR-6090" as used in this specification include the hsa-miR-6090 gene described in sequence number 224 (miRBase accession number MIMAT0023715), homologs or orthologs of other species, etc. The hsa-miR-6090 gene can be obtained using the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Furthermore, as a precursor to "hsa-miR-6090," "hsa-mir-6090" (miRBase accession number MI0020367, sequence number 445), which forms a hairpin-like structure, is known.

[0351] The terms "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" as used in this specification include the hsa-miR-6757-5p gene described in sequence number 714 (miRBase accession number MIMAT0027414), homologs or orthologs of other species, etc. 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 to "hsa-miR-6757-5p", "hsa-mir-6757" (miRBase accession number MI0022602, sequence number 730), which forms a hairpin-like structure, is known.

[0352] The terms "hsa-miR-4448 gene" or "hsa-miR-4448" as used in this specification include the hsa-miR-4448 gene described in sequence number 715 (miRBase accession number MIMAT0018967), homologs or orthologs of other species, etc. The hsa-miR-4448 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-4448", "hsa-mir-4448" (miRBase accession number MI0016791, sequence number 731) is known to form a hairpin-like structure.

[0353] The terms "hsa-miR-671-5p gene" or "hsa-miR-671-5p" as used in this specification include the hsa-miR-671-5p gene described in sequence number 716 (miRBase accession number MIMAT0003880), homologs or orthologs of other species, etc. 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 to "hsa-miR-671-5p", "hsa-mir-671" (miRBase accession number MI0003760, sequence number 732), which forms a hairpin-like structure, is known.

[0354] The terms "hsa-miR-3178 gene" or "hsa-miR-3178" as used in this specification include the hsa-miR-3178 gene described in sequence number 717 (miRBase accession number MIMAT0015055), homologs or orthologs of other species, etc. 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 number MI0014212, sequence number 733) is known to form a hairpin-like structure.

[0355] The terms "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" as used in this specification include the hsa-miR-4725-3p gene described in sequence number 718 (miRBase accession number MIMAT0019844), homologs or orthologs of other species, etc. 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 to "hsa-miR-4725-3p", "hsa-mir-4725" (miRBase accession number MI0017362, sequence number 734), which forms a hairpin-like structure, is known.

[0356] The terms "hsa-miR-940 gene" or "hsa-miR-940" as used in this specification include the hsa-miR-940 gene described in sequence number 719 (miRBase accession number MIMAT0004983), homologs or orthologs of other species, etc. The hsa-miR-940 gene can be obtained using the method described in Lui WO et al., 2007, A Cancer Res., Vol. 67, pp. 6031-6043. Furthermore, as a precursor to "hsa-miR-940," "hsa-mir-940" (miRBase accession number MI0005762, sequence number 735), which forms a hairpin-like structure, is known.

[0357] The terms "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" as used in this specification include the hsa-miR-6789-5p gene described in sequence number 720 (miRBase accession number MIMAT0027478), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-6789-5p", "hsa-mir-6789" (miRBase accession number MI0022634, sequence number 736), which forms a hairpin-like structure, is known.

[0358] The terms "hsa-miR-4484 gene" or "hsa-miR-4484" as used in this specification include the hsa-miR-4484 gene described in sequence number 721 (miRBase accession number MIMAT0019018), homologs or orthologs of other species, etc. 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 to "hsa-miR-4484", "hsa-mir-4484" (miRBase accession number MI0016845, sequence number 737), which forms a hairpin-like structure, is known.

[0359] The terms "hsa-miR-4634 gene" or "hsa-miR-4634" as used in this specification include the hsa-miR-4634 gene described in sequence number 722 (miRBase accession number MIMAT0019691), homologs or orthologs of other species, etc. 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 to "hsa-miR-4634," "hsa-mir-4634" (miRBase accession number MI0017261, sequence number 738), which forms a hairpin-like structure, is known.

[0360] The terms "hsa-miR-4745-5p gene" or "hsa-miR-4745-5p" as used in this specification include the hsa-miR-4745-5p gene described in sequence number 723 (miRBase accession number MIMAT0019878), homologs or orthologs of other species, etc. 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. In addition, as a precursor of "hsa-miR-4745-5p", "hsa-mir-4745" (miRBase accession number MI0017384, sequence number 739) is known to form a hairpin-like structure.

[0361] The terms "hsa-miR-4730 gene" or "hsa-miR-4730" as used in this specification include the hsa-miR-4730 gene described in sequence number 724 (miRBase accession number MIMAT0019852), homologs or orthologs of other species, etc. The hsa-miR-4730 gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4730," "hsa-mir-4730" (miRBase accession number MI0017367, sequence number 740), which forms a hairpin-like structure, is known.

[0362] The terms "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" as used in this specification include the hsa-miR-6803-5p gene described in sequence number 725 (miRBase accession number MIMAT0027506), homologs or orthologs of other species, etc. The hsa-miR-6803-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6803-5p", "hsa-mir-6803" (miRBase accession number MI0022648, sequence number 741), which forms a hairpin-like structure, is known.

[0363] The terms "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" as used in this specification include the hsa-miR-6798-5p gene described in sequence number 726 (miRBase accession number MIMAT0027496), homologs or orthologs of other species, etc. The hsa-miR-6798-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, Vol. 22, pp. 1634-1645. Furthermore, as a precursor to "hsa-miR-6798-5p", "hsa-mir-6798" (miRBase accession number MI0022643, sequence number 742), which forms a hairpin-like structure, is known.

[0364] The terms "hsa-miR-3648 gene" or "hsa-miR-3648" as used in this specification include the hsa-miR-3648 gene described in sequence number 727 (miRBase accession number MIMAT0018068), homologs or orthologs of other species, etc. 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 to "hsa-miR-3648," "hsa-mir-3648" (miRBase accession number MI0016048, sequence number 743), which forms a hairpin-like structure, is known.

[0365] The terms "hsa-miR-4783-3p gene" or "hsa-miR-4783-3p" as used in this specification include the hsa-miR-4783-3p gene described in sequence number 728 (miRBase accession number MIMAT0019947), homologs or orthologs of other species, etc. The hsa-miR-4783-3p gene can be obtained using the method described in Persson H et al., 2011, Cancer Res, Vol. 71, pp. 78-86. Furthermore, as a precursor to "hsa-miR-4783-3p", "hsa-mir-4783" (miRBase accession number MI0017428, sequence number 744), which forms a hairpin-like structure, is known.

[0366] The terms "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" as used in this specification include the hsa-miR-6836-3p gene described in sequence number 729 (miRBase accession number MIMAT0027575), homologs or orthologs of other species, etc. 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. Furthermore, as a precursor to "hsa-miR-6836-3p", "hsa-mir-6836" (miRBase accession number MI0022682, sequence number 745), which forms a hairpin-like structure, is known.

[0367] Furthermore, when mature miRNAs are excised from hairpin-like RNA precursors, sometimes one or more bases before and after the sequence are cut short or long, resulting in base substitutions and creating mutants known as isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621). In miRBase version 20, in addition to the base sequences shown in sequences 1-224 and 714-729, several mutants and fragments with base sequences 446-713 and 746-765, referred to as isomiRs, are also shown. These mutants can also be obtained as miRNAs with base sequences shown in sequences 1-224 and 714-729.

[0368] That is, 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, and 94 of this invention 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 Among the polynucleotide mutants consisting of the base sequences shown in 207, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 221, 715, 716, 717, 718, 719, 721, 723, 724, 727, and 728, or the polynucleotide sequences in which u is t, the longest mutant is, for example, registered in miRBase version 20.The following serial numbers can be cited: 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 The polynucleotides are 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.

[0369] Furthermore, 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 of this invention are also present. 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 Among the polynucleotide mutants consisting of the base sequences shown in 207, 210, 211, 212, 213, 214, 215, 217, 218, 219, 220, 221, 715, 716, 717, 718, 719, 721, 723, 724, 727, and 728, or the polynucleotide sequences in which u is t, the shortest mutant is, for example, registered in miRBase version 20.The following serial numbers can be cited as examples: 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 The polynucleotide sequences shown are 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.

[0370] In addition to these mutants and fragments, several polynucleotides of isomiR registered in miRBase with sequence numbers 1–224 and 714–729 can be cited as examples. Furthermore, as examples of polynucleotides containing the base sequences shown in any of the sequences 1–224 and 714–729, polynucleotides shown in any of the sequences 225–445 and 730–745 as precursors can be cited respectively.

[0371] The names of the genes shown in sequence numbers 1 to 765 and their miRBase accession numbers are recorded in Table 1.

[0372] In this specification, "capable of specific binding" means that the nucleic acid probes or primers used in this invention bind to specific target nucleic acids, but cannot actually bind to other nucleic acids.

[0373] [Table 1]

[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 forms the basis of the priority of this application.

[0396] The effects of the invention

[0397] This invention enables easy and highly accurate detection of liver cancer. For example, by using the measurements of several miRNAs in the patient's blood, serum, and / or plasma, which can be collected in a minimally invasive manner, it is easy to determine whether the patient has liver cancer. Attached Figure Description

[0398] Figure 1 The diagram illustrates the relationship between the base sequences of hsa-miR-1343-5p (as shown in sequence number 131) and hsa-miR-1343-3p (as shown in sequence number 1), generated from hsa-miR-1343 (as shown in sequence number 225) as a precursor.

[0399] Figure 2 Left panel: A graph with the hsa-miR-1343-3p (serial number 1) measurements in healthy individuals (100 people) and liver cancer patients (34 people) selected as the learning specimen group, plotted on the vertical axis. The horizontal line in the graph represents the threshold (7.09) optimized by Fisher's discriminant analysis to distinguish between the two groups. Right panel: A graph with the hsa-miR-1343-3p (serial number 1) measurements in healthy individuals (50 people) and liver cancer patients (16 people) selected as the test specimen group, plotted on the vertical axis. The horizontal line in the graph represents the threshold (7.09) set for the learning specimen group to distinguish between the two groups.

[0400] Figure 3 Left panel: A graph showing the hsa-miR-1343-3p (serial number 1) measurements in healthy individuals (100 people, circles) and liver cancer patients (34 people, triangles) selected as the study subjects, with the hsa-miR-6726-5p (serial number 2) measurements on the y-axis. The lines in the graph represent the discriminant function (0 = 0.77x + y - 15.07) optimized by Fisher's discriminant analysis to distinguish between the two groups. Right panel: A graph showing the hsa-miR-1343-3p (serial number 1) measurements in healthy individuals (50 people, circles) and liver cancer patients (16 people, triangles) selected as the test subjects, with the hsa-miR-6726-5p (serial number 2) measurements on the y-axis. The lines in the figure represent the threshold set by the learning specimen group to distinguish between the two groups (0 = 0.77x + y - 15.07).

[0401] Figure 4Top-middle image: The study subjects included 35 patients with liver cancer, 99 healthy individuals, 72 patients with pancreatic cancer, 61 patients with biliary tract cancer, 35 patients with colorectal cancer, 38 patients with gastric cancer, 25 patients with esophageal cancer, and 16 patients with benign pancreatic and biliary tract diseases. The study samples included hsa-miR-6131 (serial number 7), hsa-miR-642a-3p (serial number 148), hsa-miR-7641 (serial number 9), and hsa- The measured value of miR-6729-5p (serial number 27) was determined using Fisher's discriminant analysis to generate a discriminant formula (0.88xhsa-miR-6131-1.58xhas-miR-642a-3p+0.39xhsa-miR-7641-0.33xhsa-miR-6729-5p+5.19). A graph was plotted with the discriminant score obtained from this formula on the ordinate and the sample group on the x-axis. The dashed line in the graph represents the discriminant boundary between the two groups where the discriminant score is 0. The following figure shows the hsa-miR-6131 (serial number 7), hsa-miR-642a-3p (serial number 148), hsa-miR-7641 (serial number 9), and hsa-miR-6729-5p (serial number 27) measurements relative to the discriminant scores obtained from the discriminant formula derived by the learning specimen group on the vertical axis and the specimen group on the horizontal axis, relative to the measured values ​​of hsa-miR-6131 (serial number 7), hsa-miR-642a-3p (serial number 148), hsa-miR-7641 (serial number 9), and hsa-miR-6729-5p (serial number 27) in the selected test specimen groups (17 liver cancer patients, 51 healthy individuals, 28 pancreatic cancer patients, 37 biliary tract cancer patients, 15 colorectal cancer patients, 12 gastric cancer patients, 25 esophageal cancer patients, and 5 patients with benign pancreatic and biliary diseases). The dashed lines in the figure represent the discriminant boundary between the two groups where the discriminant score is 0. Detailed Implementation

[0402] The present invention will be further described in detail below.

[0403] 1. Target nucleic acids for liver cancer

[0404] For use with the nucleic acid probes or primers defined above for liver cancer detection of the present invention, the main target nucleic acids that serve as liver cancer markers for detecting the presence and / or absence of liver cancer or liver cancer cells can be selected from 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-m 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-67&82-5p, 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-67&98-5p, 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 miRNA selected from 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 preferred as a target nucleic acid. Further, other liver cancer markers that can be combined with these miRNAs, namely, those selected from 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, and 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 R-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 preferred as target nucleic acids.

[0405] Among the above-mentioned miRNAs, for example, a human gene containing the base sequence 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-4258hsa-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, h 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 transcripts, and their mutants or derivatives. Here, genes, homologs, transcripts, mutants, and derivatives are as defined above.

[0406] The preferred target nucleic acid is a human gene containing the base sequence shown in any one of the sequence numbers 1 to 765, or its transcript, more preferably the transcript, i.e., miRNA, pri-miRNA or pre-miRNA as its precursor RNA.

[0407] The primary target genes are the hsa-miR-1343-3p gene, their homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0408] The second target gene is the hsa-miR-6726-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0409] The third target gene is the hsa-miR-6515-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0410] The fourth target gene is the hsa-miR-4651 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0411] The fifth target gene is the hsa-miR-4257 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0412] The sixth target gene is the hsa-miR-3188 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0413] The seventh target gene is the hsa-miR-6131 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0414] The eighth target gene is the hsa-miR-6766-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0415] The ninth target gene is the hsa-miR-7641 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0416] The 10th target gene is the hsa-miR-1249 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0417] The 11th target gene is the hsa-miR-3679-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0418] The 12th target gene is the hsa-miR-6787-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0419] The 13th target gene is the hsa-miR-4454 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0420] The 14th target gene is the hsa-miR-3135b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0421] The 15th target gene is the hsa-miR-6765-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0422] The 16th target gene is the hsa-miR-7975 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0423] The 17th target gene is the hsa-miR-204-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0424] The 18th target gene is the hsa-miR-7977 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0425] The 19th target gene is the hsa-miR-7110-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0426] The 20th target gene is the hsa-miR-6717-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0427] The 21st target gene is the hsa-miR-6870-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0428] The 22nd target gene is the hsa-miR-663b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0429] The 23rd target gene is the hsa-miR-6875-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0430] The 24th target gene is the hsa-miR-8072 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0431] The 25th target gene is the hsa-miR-6816-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0432] The 26th target gene is the hsa-miR-4281 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0433] The 27th target gene is the hsa-miR-6729-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0434] The 28th target gene is the hsa-miR-8069 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0435] The 29th target gene is the hsa-miR-4706 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0436] The 30th target gene is the hsa-miR-7108-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0437] The 31st target gene is the hsa-miR-4433b-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0438] The 32nd target gene is the hsa-miR-6893-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0439] The 33rd target gene is the hsa-miR-6857-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0440] The 34th target gene is the hsa-miR-1227-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0441] The 35th target gene is the hsa-miR-6741-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0442] The 36th target gene is the hsa-miR-451a gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0443] The 37th target gene is the hsa-miR-8063 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0444] The 38th target gene is the hsa-miR-3622a-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0445] The 39th target gene is the hsa-miR-615-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0446] The 40th target gene is the hsa-miR-128-1-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0447] The 41st target gene is the hsa-miR-6825-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0448] The 42nd target gene is the hsa-miR-1260b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0449] The 43rd target gene is the hsa-miR-4433-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0450] The 44th target gene is the hsa-miR-4665-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0451] The 45th target gene is the hsa-miR-7845-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0452] The 46th target gene is the hsa-miR-1908-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0453] The 47th target gene is the hsa-miR-6840-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0454] The 48th target gene is the hsa-miR-6765-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0455] The 49th target gene is the hsa-miR-296-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0456] The 50th target gene is the hsa-miR-3675-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0457] The 51st target gene is the hsa-miR-6781-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0458] The 52nd target gene is the hsa-miR-423-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0459] The 53rd target gene is the hsa-miR-3663-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0460] The 54th target gene is the hsa-miR-6784-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0461] The 55th target gene is the hsa-miR-6749-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0462] The 56th target gene is the hsa-miR-1231 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0463] The 57th target gene is the hsa-miR-4746-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0464] The 58th target gene is the hsa-miR-6780b-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0465] The 59th target gene is the hsa-miR-4758-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0466] The 60th target gene is the hsa-miR-3679-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0467] The 61st target gene is the hsa-miR-3184-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0468] The 62nd target gene is the hsa-miR-6125 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0469] The 63rd target gene is the hsa-miR-6721-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0470] The 64th target gene is the hsa-miR-6791-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0471] The 65th target gene is the hsa-miR-3185 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0472] The 66th target gene is the hsa-miR-1260a gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0473] The 67th target gene is the hsa-miR-3197 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0474] The 68th target gene is the hsa-miR-6845-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0475] The 69th target gene is the hsa-miR-6887-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0476] The 70th target gene is the hsa-miR-6738-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0477] The 71st target gene is the hsa-miR-6872-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0478] The 72nd target gene is the hsa-miR-4497 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0479] The 73rd target gene is the hsa-miR-1229-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0480] The 74th target gene is the hsa-miR-6820-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0481] The 75th target gene is the hsa-miR-6777-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0482] The 76th target gene is the hsa-miR-3917 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0483] The 77th target gene is the hsa-miR-5787 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0484] The 78th target gene is the hsa-miR-4286 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0485] The 79th target gene is the hsa-miR-6877-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0486] The 80th target gene is the hsa-miR-1225-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0487] The 81st target gene is the hsa-miR-6088 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0488] The 82nd target gene is the hsa-miR-6800-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0489] The 83rd target gene is the hsa-miR-1246 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0490] The 84th target gene is the hsa-miR-4467 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0491] The 85th target gene is the hsa-miR-4419b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0492] The 86th target gene is the hsa-miR-1914-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0493] The 87th target gene is the hsa-miR-4632-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0494] The 88th target gene is the hsa-miR-1915-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0495] The 89th target gene is the hsa-miR-3940-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0496] The 90th target gene is the hsa-miR-1185-2-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0497] The 91st target gene is the hsa-miR-6746-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0498] The 92nd target gene is the hsa-miR-5001-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0499] The 93rd target gene is the hsa-miR-1228-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0500] The 94th target gene is the hsa-miR-5572 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0501] The 95th target gene is the hsa-miR-4327 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0502] The 96th target gene is the hsa-miR-4638-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0503] The 97th target gene is the hsa-miR-6799-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0504] The 98th target gene is the hsa-miR-6861-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0505] The 99th target gene is the hsa-miR-6727-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0506] The 100th target gene is the hsa-miR-4513 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0507] The 101st target gene is the hsa-miR-6805-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0508] The 102nd target gene is the hsa-miR-6808-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0509] The 103rd target gene is the hsa-miR-4449 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0510] The 104th target gene is the hsa-miR-1199-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0511] The 105th target gene is the hsa-miR-1275 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0512] The 106th target gene is the hsa-miR-4792 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0513] The 107th target gene is the hsa-miR-4443 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0514] The 108th target gene is the hsa-miR-6891-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0515] The 109th target gene is the hsa-miR-6826-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0516] The 110th target gene is the hsa-miR-6807-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0517] The 111th target gene is the hsa-miR-7150 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0518] The 112th target gene is the hsa-miR-4534 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0519] The 113th target gene is the hsa-miR-4476 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0520] The 114th target gene is the hsa-miR-4649-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0521] The 115th target gene is the hsa-miR-4525 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0522] The 116th target gene is the hsa-miR-1915-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0523] The 117th target gene is the hsa-miR-4516 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0524] The 118th target gene is the hsa-miR-4417 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0525] The 119th target gene is the hsa-miR-642b-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0526] The 120th target gene is the hsa-miR-3141 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0527] The 121st target gene is the hsa-miR-5100 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0528] The 122nd target gene is the hsa-miR-6848-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0529] The 123rd target gene is the hsa-miR-4739 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0530] The 124th target gene is the hsa-miR-4459 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0531] The 125th target gene is the hsa-miR-1237-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0532] The 126th target gene is the hsa-miR-296-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0533] The 127th target gene is the hsa-miR-4665-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0534] The 128th target gene is the hsa-miR-6786-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0535] The 129th target gene is the hsa-miR-4258 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0536] The 130th target gene is the hsa-miR-6510-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0537] The 131st target gene is the hsa-miR-1343-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0538] The 132nd target gene is the hsa-miR-1247-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0539] The 133rd target gene is the hsa-miR-6805-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0540] The 134th target gene is the hsa-miR-4492 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0541] The 135th target gene is the hsa-miR-1469 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0542] The 136th target gene is the hsa-miR-1268b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0543] The 137th target gene is the hsa-miR-6858-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0544] The 138th target gene is the hsa-miR-3937 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0545] The 139th target gene is the hsa-miR-939-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0546] The 140th target gene is the hsa-miR-3656 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0547] The 141st target gene is the hsa-miR-744-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0548] The 142nd target gene is the hsa-miR-4687-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0549] The 143rd target gene is the hsa-miR-4763-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0550] The 144th target gene is the hsa-miR-3620-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0551] The 145th target gene is the hsa-miR-3195 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0552] The 146th target gene is the hsa-miR-6842-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0553] The 147th target gene is the hsa-miR-4707-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0554] The 148th target gene is the hsa-miR-642a-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0555] The 149th target gene is the hsa-miR-7113-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0556] The 150th target gene is the hsa-miR-4728-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0557] The 151st target gene is the hsa-miR-5195-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0558] The 152nd target gene is the hsa-miR-1185-1-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0559] The 153rd target gene is the hsa-miR-6774-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0560] The 154th target gene is the hsa-miR-8059 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0561] The 155th target gene is the hsa-miR-3131 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0562] The 156th target gene is the hsa-miR-7847-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0563] The 157th target gene is the hsa-miR-4463 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0564] The 158th target gene is the hsa-miR-128-2-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0565] The 159th target gene is the hsa-miR-4508 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0566] The 160th target gene is the hsa-miR-6806-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0567] The 161st target gene is the hsa-miR-7111-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0568] The 162nd target gene is the hsa-miR-6782-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0569] The 163rd target gene is the hsa-miR-4734 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0570] The 164th target gene is the hsa-miR-3162-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0571] The 165th target gene is the hsa-miR-887-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0572] The 166th target gene is the hsa-miR-6752-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0573] The 167th target gene is the hsa-miR-6724-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0574] The 168th target gene is the hsa-miR-23b-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Documents 2 and 3).

[0575] The 169th target gene is the hsa-miR-23a-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0576] The 170th target gene is the hsa-miR-625-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 4).

[0577] The 171st target gene is the hsa-miR-1228-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0578] The 172nd target gene is the hsa-miR-614 gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0579] The 173rd target gene is the hsa-miR-1913 gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 4).

[0580] The 174th target gene is the hsa-miR-92a-2-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 1).

[0581] The 175th target gene is the hsa-miR-187-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 5).

[0582] The 176th target gene is the hsa-miR-16-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Documents 4 and 5).

[0583] The 177th target gene is the hsa-miR-92b-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 1).

[0584] The 178th target gene is the hsa-miR-150-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0585] The 179th target gene is the hsa-miR-564 gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0586] The 180th target gene is the hsa-miR-125a-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 3).

[0587] The 181st target gene is the hsa-miR-92b-5p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 1).

[0588] The 182nd target gene is the hsa-miR-92a-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 1, Patent Document 4, and Patent Document 5).

[0589] The 183rd target gene is the hsa-miR-663a gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 4).

[0590] The 184th target gene is the hsa-miR-4688 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0591] The 185th target gene is the hsa-miR-4648 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0592] The 186th target gene is the hsa-miR-6085 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0593] The 187th target gene is the hsa-miR-6126 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0594] The 188th target gene is the hsa-miR-6880-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0595] The 189th target gene is the hsa-miR-328-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0596] The 190th target gene is the hsa-miR-6768-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0597] The 191st target gene is the hsa-miR-3180 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0598] The 192nd target gene is the hsa-miR-6087 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0599] The 193rd target gene is the hsa-miR-1273g-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0600] The 194th target gene is the hsa-miR-1225-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0601] The 195th target gene is the hsa-miR-3196 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0602] The 196th target gene is the hsa-miR-4695-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0603] The 197th target gene is the hsa-miR-6732-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0604] The 198th target gene is the hsa-miR-638 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0605] The 199th target gene is the hsa-miR-6813-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0606] The 200th target gene is the hsa-miR-665 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0607] The 201st target gene is the hsa-miR-486-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Documents 2 and 3).

[0608] The 202nd target gene is the hsa-miR-4466 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0609] The 203rd target gene is the hsa-miR-30c-1-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Documents 3 and 5).

[0610] The 204th target gene is the hsa-miR-3621 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0611] The 205th target gene is the hsa-miR-6743-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0612] The 206th target gene is the hsa-miR-4298 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0613] The 207th target gene is the hsa-miR-4741 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0614] The 208th target gene is the hsa-miR-3619-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0615] The 209th target gene is the hsa-miR-6824-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0616] The 210th target gene is the hsa-miR-5698 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0617] The 211th target gene is the hsa-miR-371a-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0618] The 212th target gene is the hsa-miR-4488 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0619] The 213th target gene is the hsa-miR-1233-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0620] The 214th target gene is the hsa-miR-4723-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0621] The 215th target gene is the hsa-miR-24-3p gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0622] The 216th target gene is the hsa-miR-1238-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0623] The 217th target gene is the hsa-miR-4442 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0624] The 218th target gene is the hsa-miR-3928-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0625] The 219th target gene is the hsa-miR-6716-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0626] The 220th target gene is the hsa-miR-6089 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0627] The 221st target gene is the hsa-miR-6124 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0628] The 222nd target gene is the hsa-miR-6778-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0629] The 223rd target gene is the hsa-miR-557 gene, its homologs, their transcripts, or their mutants or derivatives. Reports to date that changes in the expression of this gene or its transcripts can serve as biomarkers for liver cancer are known (Patent Document 2).

[0630] The 224th target gene is the hsa-miR-6090 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in the expression of this gene or its transcripts serving as biomarkers for liver cancer.

[0631] The 225th target gene is the hsa-miR-6757-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0632] The 226th target gene is the hsa-miR-4448 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0633] The 227th target gene is the hsa-miR-671-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0634] The 228th target gene is the hsa-miR-3178 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0635] The 229th target gene is the hsa-miR-4725-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0636] The 230th target gene is the hsa-miR-940 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0637] The 231st target gene is the hsa-miR-6789-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0638] The 232nd target gene is the hsa-miR-4484 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0639] The 233rd target gene is the hsa-miR-4634 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0640] The 234th target gene is the hsa-miR-4745-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0641] The 235th target gene is the hsa-miR-4730 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0642] The 236th target gene is the hsa-miR-6803-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0643] The 237th target gene is the hsa-miR-6798-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0644] The 238th target gene is the hsa-miR-3648 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0645] The 239th target gene is the hsa-miR-4783-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0646] The 240th target gene is the hsa-miR-6836-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there are no reports of changes in gene or transcript expression serving as biomarkers for liver cancer.

[0647] 2. Nucleic acid probes or primers used for liver cancer detection

[0648] In this invention, nucleic acids that can specifically bind to the target nucleic acids described above as liver cancer markers can be used as nucleic acids for detecting or diagnosing liver cancer, such as nucleic acid probes or primers.

[0649] In this invention, nucleic acid probes or primers capable of detecting or diagnosing liver cancer can qualitatively and / or quantitatively determine the presence, expression level, or quantity of the target nucleic acids used as liver cancer markers. These target nucleic acids include, for example, 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, and 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-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-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-4665-3phsa-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 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 combinations thereof, or their homologs, their transcripts, their mutants or derivatives, 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, which may be combined with them as appropriate.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 combinations thereof, or their homologs, their transcripts, their mutants or derivatives, and hsa-miR-4688, hsa-miR-4, which may be combined with them 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 combinations thereof, or their homologs, their transcripts, their mutants, or their derivatives.

[0650] Regarding the aforementioned target nucleic acids, compared to healthy individuals, their expression levels in subjects with liver cancer can be either increased or decreased (hereinafter referred to as "increased / decreased"), depending on the type of target nucleic acid. Therefore, the nucleic acid of the present invention can measure the expression levels of the aforementioned target nucleic acids in bodily fluids derived from subjects suspected of having liver cancer (e.g., humans) and bodily fluids derived from healthy individuals, and compare them, thus effectively detecting liver cancer.

[0651] The nucleic acid probes or primers that can be used in this invention are nucleic acid probes that can specifically bind to polynucleotides composed of at least one of the base sequences shown in sequence numbers 1-167 and 714-729, or primers for amplifying polynucleotides composed of at least one of the base sequences shown in sequence numbers 1-167 and 714-729.

[0652] The nucleic acid probes or primers that can be used in this invention may further include nucleic acid probes that can specifically bind to polynucleotides composed of at least one of the base sequences shown in sequence numbers 168-183, or primers for amplifying polynucleotides composed of at least one of the base sequences shown in sequence numbers 168-183.

[0653] The nucleic acid probes or primers that can be used in this invention may further include nucleic acid probes that can specifically bind to polynucleotides composed of at least one of the base sequences shown in sequence numbers 184 to 224, or primers for amplifying polynucleotides composed of at least one of the base sequences shown in sequence numbers 184 to 224.

[0654] Specifically, the aforementioned nucleic acid probes or primers comprise polynucleotide groups selected from the base sequences shown in any one of the sequence numbers 1 to 765, or base sequences in which u is t, and their complementary polynucleotide groups; polynucleotide groups and their complementary polynucleotide groups that hybridize separately to DNA composed of base sequences complementary to the aforementioned base sequences under stringent conditions (described later); and combinations of one or more polynucleotides contained in polynucleotide groups comprising 15 or more, preferably 17 or more consecutive bases in the base sequences of these polynucleotide groups. These polynucleotides can be used as nucleic acid probes and primers for detecting the aforementioned liver cancer markers as target nucleic acids.

[0655] More specifically, examples of nucleic acid probes or primers that can be used in this invention are one or more polynucleotides selected from the following polynucleotides (a) to (e).

[0656] (a) A polynucleotide consisting of 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, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0657] (b) A polynucleotide containing the base sequence shown in any of the sequence numbers 1–167 and 714–729.

[0658] (c) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 1-167 and 714-729, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0659] (d) A polynucleotide containing a base sequence complementary to the base sequence shown in any of the sequences 1–167 and 714–729, or a base sequence in which u is t, and

[0660] (e) A polynucleotide that hybridizes with any of the polynucleotides (a) to (d) above under strict conditions.

[0661] The nucleic acid probes or primers that can be used in this invention may further contain polynucleotides selected from the polynucleotides shown in (f) to (j) below, in addition to at least one polynucleotide selected from the polynucleotides (a) to (e) above.

[0662] (f) A polynucleotide consisting of the base sequence shown in any of the sequence numbers 168 to 183, or a sequence of bases in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0663] (g) A polynucleotide containing the base sequence shown in any of the sequence numbers 168–183.

[0664] (h) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 168-183, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0665] (i) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequence numbers 168–183, or a base sequence in which u is t, and

[0666] (j) A polynucleotide that hybridizes with any of the polynucleotides (f) to (i) above under strict conditions.

[0667] The nucleic acid probes or primers that can be used in this invention may further contain polynucleotides selected from the polynucleotides shown in (k) to (o) below, in addition to at least one polynucleotide selected from the polynucleotides (a) to (j) above.

[0668] (k) A polynucleotide consisting of a base sequence represented by any one of sequence numbers 184 to 224, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0669] (l) A polynucleotide containing the base sequence shown in any of the sequence numbers 184 to 224.

[0670] (m) A polynucleotide consisting of a base sequence complementary to the base sequence shown in any of the sequence numbers 184 to 224, or a base sequence in which u is t, a mutant of the polynucleotide, a derivative of the polynucleotide, or a fragment of the polynucleotide containing 15 or more consecutive bases.

[0671] (n) A polynucleotide containing a base sequence complementary to the base sequence shown in any of sequence numbers 184–224, or a base sequence in which u is t, and

[0672] (o) is a polynucleotide that hybridizes with any of the polynucleotides (k) to (n) above under strict conditions.

[0673] The term "fragment containing 15 or more consecutive bases" in the above-mentioned polynucleotide can be included in the range of bases in the base sequence of each polynucleotide, such as 15 or less, 17 or less, or 19 or less, but is not limited to this range.

[0674] Any of the above-mentioned polynucleotides or their fragments used in this invention can be DNA or RNA.

[0675] The polynucleotides used in this invention can be produced using common techniques such as DNA recombination technology, PCR, and methods using an automated DNA / RNA synthesizer.

[0676] DNA recombination technology and PCR can use techniques described in, for example, 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).

[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 in 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-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-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 R-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 their methods of acquisition are also known, as described above. Therefore, by cloning this gene, polynucleotides that can be used as nucleic acid probes or primers in this invention can be produced.

[0678] Such nucleic acid probes or primers can be chemically synthesized using automated DNA synthesis devices. This synthesis typically employs the phosphoramidite method, which can automatically synthesize single-stranded DNA up to approximately 100 base pairs. Automated DNA synthesis devices are commercially available from companies such as Polygen, ABI, and Applied BioSystems.

[0679] Alternatively, the polynucleotides of the present invention can also be prepared by cDNA cloning. cDNA cloning technology can utilize, for example, the Wako microRNA Cloning Kit.

[0680] Here, the sequences of nucleic acid probes and primers used to detect polynucleotides composed of the base sequences shown in any of the sequences 1–224 and 714–729 are not present in vivo as miRNAs or their precursors. For example, the base sequences shown in sequences 1 and 131 are generated from the precursor shown in sequence 225, but this precursor has… Figure 1 The hairpin-like structure shown has mismatched base sequences in sequence numbers 1 and 131. Therefore, base sequences that are completely complementary to those shown in sequence number 1 or 131 are not naturally generated in vivo. Similarly, the nucleic acid probes and primers used to detect the base sequences shown in any of sequences 1–224 and 714–729 have artificial base sequences that are not present in vivo.

[0681] 3. Reagent kits or devices for liver cancer detection

[0682] The present invention also provides a kit or device for detecting liver cancer comprising one or more polynucleotides (which may contain mutants, fragments or derivatives; hereinafter sometimes referred to as detection polynucleotides) that are used in the present invention as nucleic acid probes or primers for determining target nucleic acids as biomarkers of liver cancer.

[0683] The target nucleic acids used as biomarkers for liver cancer in this invention are preferably selected from 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-1185-2-3pmiR-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 circumstances, the additional target nucleic acids that can be used for assay 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] Further target nucleic acids that may be used for assaying, depending on the circumstances, are 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 contains a nucleic acid capable of specifically binding to the target nucleic acid described above as a biomarker for liver cancer, preferably the nucleic acid probe or primer described in section 2 above, specifically one or more polynucleotides or mutants thereof selected from the polynucleotide classes described in section 2 above.

[0688] Specifically, the kit or device of the present invention may contain at least one of the following: a polynucleotide containing a base sequence shown in any one of the sequence numbers 1 to 167 and 714 to 729 or a base sequence in which u is t (or composed of a base sequence shown in any one of the sequence numbers 1 to 235 and 851 to 856 or a base sequence in which u is t), a polynucleotide containing its complementary sequence (or composed of its complementary sequence), a polynucleotide hybridizing with these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences containing 15 or more consecutive bases.

[0689] The kit or device of the present invention may further comprise one or more of the following: a polynucleotide comprising the base sequence shown in any of the serial numbers 168 to 183 or a base sequence in which u is t (or composed of the base sequence shown in any of the serial numbers 168 to 183 or a base sequence in which u is t), a polynucleotide comprising its complementary sequence (or composed of its complementary sequence), a polynucleotide hybridizing with 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 comprise one or more of the following: a polynucleotide comprising the base sequence shown in any of the serial numbers 184 to 224 or a base sequence in which u is t (or composed of the base sequence shown in any of the serial numbers 184 to 224 or a base sequence in which u is t), a polynucleotide comprising its complementary sequence (or composed of its complementary sequence), a polynucleotide hybridizing with these polynucleotides under stringent conditions, or a mutant or fragment of these polynucleotide sequences comprising 15 or more consecutive bases.

[0691] The kit or device of the present invention may contain fragments, for example, one or more, preferably two or more, polynucleotides selected from (1) to (3) below.

[0692] (1) A polynucleotide containing 15 or more consecutive bases in a base sequence of u=t or its complementary sequence as shown in any of the sequence numbers 1 to 167 and 714 to 729.

[0693] (2) A polynucleotide containing 15 or more consecutive bases in a base sequence of u=t or its complementary sequence shown in any of the sequence numbers 168 to 183.

[0694] (3) A polynucleotide containing 15 or more consecutive bases in a base sequence of u=t or its complementary sequence shown in any of the sequence numbers 184 to 224.

[0695] In a preferred embodiment, the polynucleotide is a polynucleotide composed of 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; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant of these polynucleotides containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.

[0696] Furthermore, in a preferred embodiment, the polynucleotide is a polynucleotide composed of a base sequence shown in any one of serial numbers 168 to 183 or a base sequence in which u is t; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant of these polynucleotides containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.

[0697] Furthermore, in a preferred embodiment, the polynucleotide is a polynucleotide composed of a base sequence shown in any one of serial numbers 184 to 224 or a base sequence in which u is t; a polynucleotide composed of its complementary sequence; a polynucleotide that hybridizes with these polynucleotides under stringent conditions; or a mutant of these polynucleotides containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.

[0698] In a preferred embodiment, the above-mentioned fragment may be a polynucleotide containing 15 or more, preferably 17 or more, and more preferably 19 or more consecutive bases.

[0699] In this invention, the size of the polynucleotide fragment is, for example, within the range of 15 to less than the total number of bases in the sequence of each polynucleotide, 17 to less than the total number of bases in the sequence, 19 to less than the total number of bases in the sequence, etc.

[0700] Specifically, examples of the above-described polynucleotide combinations constituting the kits or devices of the present invention include any combination of the above-described polynucleotides consisting of the base sequences represented by the sequence numbers shown in Table 1 (sequence numbers 1-224 and 714-729 corresponding to the miRNA markers in Table 1) or their complementary sequences. These are strictly illustrative, and all other possible combinations are included in the present invention.

[0701] For example, in the present invention, as a combination constituting a kit or device for distinguishing between liver cancer and healthy individuals, it is desirable to combine the polynucleotides composed of the base sequences represented by the serial numbers shown in Table 1 in two or more combinations. Generally, a combination of two can achieve sufficient performance.

[0702] Specifically, the combination of two polynucleotides consisting of a base sequence or its complementary sequence used to distinguish between liver cancer and a healthy body is selected from the combination of two of the above-mentioned polynucleotides consisting of base sequences represented by sequence numbers 1 to 224 and 714 to 729, and preferably includes at least one newly discovered polynucleotide consisting of a base sequence represented by sequence numbers 1 to 167 and 714 to 729.

[0703] Furthermore, the preferred combination of polynucleotides, which is cancer-type specific and can distinguish not only liver cancer from healthy individuals but also from other cancers, is selected from sequence numbers 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, and 166. A combination of at least one polynucleotide from a group consisting of polynucleotides 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, this group is designated as "cancer type-specific polynucleotide group 1"), and a combination of multiple polynucleotides of other sequence numbers.

[0704] Furthermore, as a combination of cancer-type-specific polynucleotides that can not only distinguish between liver cancer and healthy individuals but also between liver cancer and other cancers, it is more preferably a combination of multiple polynucleotides selected from cancer-type-specific polynucleotide group 1.

[0705] Furthermore, as a combination of polynucleotides with cancer type specificity that can not only distinguish between liver cancer and healthy individuals but also between liver cancer and 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 comprising at least one polynucleotide selected from the polynucleotide 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 or their complementary sequences contained in cancer type specific polynucleotide group 1 (hereinafter, this group is referred to as "cancer type specific polynucleotide group 2").

[0706] The number of the aforementioned combinations of cancer-type specific polynucleotides can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, more preferably 4 or more, and generally, a combination of 4 can obtain sufficient performance.

[0707] Hereinafter, examples are given, without limitation, of a polynucleotide consisting of the base sequence shown in Serial No. 1 or its complementary sequence, and a polynucleotide consisting of the base sequence shown in the Serial No. 1 of three polynucleotides selected from cancer-type-specific polynucleotide group 1 or its complementary sequence.

[0708] (1) Combinations of serial numbers 1, 7, 9, 148 (markers: hsa-miR-1343-3p, hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p)

[0709] (2) Combinations of serial numbers 1, 9, 155, 172 (markers: hsa-miR-1343-3p, hsa-miR-7641, hsa-miR-3131, hsa-miR-614)

[0710] (3) Combinations of serial numbers 1, 9, 148, 155 (markers: hsa-miR-1343-3p, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-3131)

[0711] (4) Combinations of serial numbers 1, 155, 172, 715 (markers: hsa-miR-1343-3p, hsa-miR-3131, hsa-miR-614, hsa-miR-4448)

[0712] (5) Combinations of serial numbers 1, 155, 164, 715 (markers: hsa-miR-1343-3p, hsa-miR-3131, hsa-miR-3162-5p, hsa-miR-4448)

[0713] Furthermore, the following examples, without limitation, illustrate combinations of polynucleotides consisting of the base sequence shown in sequence number 3 or its complementary sequence, and polynucleotides consisting of the base sequence shown in the sequence number of the three polynucleotides selected from cancer-type-specific polynucleotide group 1 or its complementary sequence.

[0714] (1) Combinations of serial numbers 3, 7, 9, 148 (markers: hsa-miR-6515-3p, hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p)

[0715] (2) Combinations of serial numbers 3, 22, 27, 46 (markers: hsa-miR-6515-3p, hsa-miR-663b, hsa-miR-6729-5p, hsa-miR-1908-5p)

[0716] (3) Combinations of serial numbers 1, 3, 29, 155 (markers: hsa-miR-1343-3p, hsa-miR-6515-3p, hsa-miR-4706, hsa-miR-3131)

[0717] (4) Combinations of serial numbers 1, 3, 151, 155 (markers: hsa-miR-1343-3p, hsa-miR-6515-3p, hsa-miR-5195-3p, hsa-miR-3131)

[0718] (5) Combinations of serial numbers 3, 7, 148, 715 (markers: hsa-miR-6515-3p, hsa-miR-6131, hsa-miR-642a-3p, hsa-miR-4448)

[0719] Furthermore, the following examples, without limitation, illustrate combinations of polynucleotides consisting of the base sequence shown in Serial Number 7 or its complementary sequence, and polynucleotides consisting of the base sequence shown in the sequence number of the three polynucleotides selected from cancer-type-specific polynucleotide group 1, or their complementary sequences.

[0720] (1) Combinations of serial numbers 7, 28, 148, 717 (markers: hsa-miR-6131, hsa-miR-8069, hsa-miR-642a-3p, hsa-miR-3178)

[0721] (2) Combinations of serial numbers 7, 9, 148, 186 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-6085)

[0722] (3) Combinations of serial numbers 7, 148, 172, 715 (markers: hsa-miR-6131, hsa-miR-642a-3p, hsa-miR-614, hsa-miR-4448)

[0723] (4) Combinations of serial numbers 7, 9, 148, 723 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-4745-5p)

[0724] (5) Combinations of serial numbers 7, 9, 28, 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-8069, hsa-miR-642a-3p)

[0725] Furthermore, the following examples, without limitation, illustrate combinations of polynucleotides consisting of the base sequence shown in Serial Number 9 or its complementary sequence, and polynucleotides consisting of the base sequence shown in the sequence number of the three polynucleotides selected from cancer-type-specific polynucleotide groups 1, or their complementary sequences.

[0726] (1) Combinations of serial numbers 7, 9, 148, 157 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-4463)

[0727] (2) Combinations of serial numbers 7, 9, 148, 722 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-4634)

[0728] (3) Combinations of serial numbers 7, 9, 27, 148 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-6729-5p, hsa-miR-642a-3p)

[0729] (4) Combinations of serial numbers 7, 9, 148, 725 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-6803-5p)

[0730] (5) Combinations of serial numbers 7, 9, 148, 729 (markers: hsa-miR-6131, hsa-miR-7641, hsa-miR-642a-3p, hsa-miR-6836-3p)

[0731] Furthermore, the following examples, without limitation, illustrate combinations of polynucleotides consisting of the ba...

Claims

1. Capable of binding to a selected one 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-3185, hsa-miR-1260a, which are liver cancer markershsa-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, hs a-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, and hsa-miR-12 46, 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, and 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-6727-5 p, 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, and hsa-miR-6 891-5p, 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 sa-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, and 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, and hsa-miR-6805-5phsa-miR-4492, hsa-miR-1469, hsa-miR-1268b, hsa-miR-6858-5p, hsa-miR-3937, hsa-miR-939-5p, hsa-miR-3656, hs a-miR-744-5p, hsa-miR-4687-3p, hsa-miR-4763-3p, hsa-miR-3620-5p, hsa-miR-3195, hsa-miR-6842-5p, hsa-miR-4 707-5p, hsa-miR-642a-3p, hsa-miR-7113-3p, hsa-miR-4728-5p, hsa-miR-5195-3p, hsa-miR-1185-1-3p, hsa-miR-67 74-5p, 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-9 40. Use of a nucleic acid that specifically binds to at least one of the polynucleotides of 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 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 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.

2. The use according to claim 1, wherein further used is a miR-23a-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-1 25a-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, 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-3 0c-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, hs a-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 (c) to (f), (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.

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