Colon cancer detection kit or device, and detection method

Abstract

To provide a colon cancer detection kit or a device, and a detection method.SOLUTION: The present invention relates to a colon cancer detection kit or a device, comprising a nucleic acid capable of specifically binding to a miRNA in a sample from a subject, and a method for detecting colon cancer, comprising measuring the miRNA in vitro.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a kit or device for detecting colorectal cancer, which contains a nucleic acid capable of specifically binding to a specific miRNA and is used for detecting the presence or absence of colorectal cancer in a subject, and a method for detecting colorectal cancer, which includes measuring the expression level of the miRNA using the nucleic acid.

Background Art

[0002] The large intestine is an organ that stores the remaining intestinal contents after digestion and absorption and forms feces while absorbing water. The large intestine starts from the cecum and then connects to the ascending colon, transverse colon, descending colon, sigmoid colon, rectum, and anal canal. According to the statistics of cancers by site in Japan in 2011 disclosed by the Cancer Countermeasure Information Center of the National Cancer Center, National Institutes of Biomedical Innovation, Health and Nutrition, the number of colorectal cancer patients is 112,772, that is, about 1 in 14 Japanese people suffers from colorectal cancer, and it is the second most common cancer site in terms of the number of patients. In addition, the number of deaths due to colorectal cancer is 45,744 for both men and women combined, and it is the third most common cancer site in terms of the number of deaths. Also, in the United States, it is said that colorectal cancer occurs in about 1 in 20 people, and the estimated number of colorectal cancer patients in the United States in 2014 is also as high as 96,830, and about 40,000 of them are said to die (Non-Patent Document 1).

[0003] The progression of colorectal cancer is defined in Non-Patent Document 2. Depending on the degree of tumor spread (Tis, T1-T4), lymph node metastasis (N0, N1a-c, N2a-b), and distant metastasis (M0, M1a-b), it is classified into Stage 0 (Tis / N0 / M0), Stage I (T1-T2 / N0 / M0), Stage II (T3-T4 / N0 / M0), Stage IIA (T3 / N0 / M0), Stage IIB (T4a / N0 / M0), Stage IIC (T4b / N0 / M0), Stage III (N1-2 / M0), Stage IIIA (T1-2 / N1 / M0 and T1 / N2a / M0), Stage IIIB (T3-T4a / N1 / M0 and T2-T3 / N2a / M0 and T1-T2 / N2b / M0), Stage IIIC (T4a / N2a / M0 and T3-T4a / N2b / M0 and T4b / N1-2 / M0), Stage IVA (M1a), and Stage IVB (M1b).

[0004] The survival rate of colorectal cancer varies depending on the progression. In Non-Patent Document 1, the following statistical values are reported separately for colon cancer and rectal cancer. The 5-year relative survival rate of colon cancer is reported as 74% for Stage I, 67% for Stage IIA, 59% for Stage IIB, 37% for Stage IIC, 73% for Stage IIIA, 46% for Stage IIIB, 28% for Stage IIIC, and 6% for Stage IV. Also, the 5-year relative survival rate of rectal cancer is reported as 74% for Stage I, 65% for Stage IIA, 52% for Stage IIB, 32% for Stage IIC, 74% for Stage IIIA, 45% for Stage IIIB, 33% for Stage IIIC, and 6% for Stage IV. From the above, colorectal cancer with a lower progression has a higher survival rate. Therefore, early detection and treatment of colorectal cancer can greatly contribute to an improvement in the survival rate.

[0005] The treatment of colorectal cancer mainly includes laparotomy and laparoscopic surgery, and chemotherapy and radiotherapy are often used in combination after surgery (Non-Patent Document 1). In particular, for early-stage colorectal cancer, endoscopic surgery that can be performed without laparotomy may be applicable.

[0006] As described in Non-Patent Document 1, fecal occult blood test and endoscopic examination are widely used for colorectal cancer screening. In particular, the fecal occult blood test is inexpensive, non-invasive, and can be performed at home. Therefore, the American Cancer Society recommends undergoing this test annually. In addition to colonoscopy, imaging tests such as barium enema, CT scan, and MRI scan are also performed to examine the location and spread of cancer. For patients already diagnosed with colorectal cancer, blood tumor marker tests such as CEA and CA19-9 may be performed for prognostic and treatment efficacy monitoring (Non-Patent Document 1).

[0007] Although still in the research stage, as shown in Patent Documents 1 to 4, there are reports of detecting colorectal cancer by measuring the expression level of microRNA (miRNA) in biological samples such as blood, or by combining the expression level of miRNA with that of other protein markers.

[0008] Patent Document 1 discloses a method for detecting colorectal cancer and other cancers using hsa-miR-92a-2-5p, hsa-miR-128-2-5p, and hsa-miR-24-3p in colorectal cancer tissues.

[0009] Patent Document 2 discloses a method for detecting colorectal cancer using hsa-miR-1233-5p and hsa-miR-1225-3p in plasma.

[0010] Patent Document 3 discloses a method for detecting colorectal cancer using multiple miRNAs such as hsa-miR-1231, hsa-miR-423-5p, and hsa-miR-1268a in colorectal tissues and feces.

[0011] Patent Document 4 discloses a method for detecting colorectal cancer using hsa-miR-150-3p and miR-92a-2-5p in tissues.

Prior Art Documents

Patent Documents

[0012] [Patent Document 1] International Publication No. 2007 / 081740 [Patent Document 2] Specification of US Patent Application Publication No. 2013 / 102487 [Patent Document 3] Specification of US Patent Application Publication No. 2012 / 088687 [Patent Document 4] Japanese Patent Publication No. 2009 - 531019 [Non - Patent Document]

[0013] [Non - Patent Document 1] American Cancer Society, "Colorectal Cancer", Revised in 2013, pp. 5 - 6, 17 - 28, 33 -, 45 - 54, 67 - 71 [Non - Patent Document 2] Sobin, L. et al., "TNM Classification of Malignant Tumours, 7th Edition", 2010, pp. 94 - 99 [Non - Patent Document 3] Allison, J.E. et al., 1996, The New England Journal of Medicine, Vol. 334(3), pp. 155 - 159 [Non - Patent Document 4] Palmqvist, R. et al., 2007, Diseases of colon and rectum, Vol. 46(11), pp. 1538 - 1544 [Summary of the Invention] [Problems to be Solved by the Invention]

[0014] An object of the present invention is to find a novel colorectal cancer tumor marker and provide a method capable of effectively detecting colorectal cancer using a nucleic acid that can specifically bind to the marker. The fecal occult blood test, which is currently widely used as a primary test for colorectal cancer, is positive even when bleeding is caused by reasons other than cancer such as hemorrhoids, while early-stage colorectal cancer without bleeding cannot be detected, and there is also a report that more than 90% of colorectal abnormalities (including cancer) are missed (Non-Patent Document 1). The specific sensitivity of the fecal occult blood test varies widely from 37% to 79.4% depending on the test kit used, and the specificity is reported to be 86.7% to 97.7% (Non-Patent Document 3). In addition, although colonoscopy is known to have high test accuracy, it is difficult to apply it to primary screening due to the need for pretreatment, sedatives, and relatively high cost (Non-Patent Document 1). Also, blood tumor markers such as CEA and CA19-9 are said not to be able to determine the presence or absence of colorectal cancer because they may increase even in cancers other than colorectal cancer. If another cancer is misdiagnosed as colorectal cancer, it will result in missing the opportunity for appropriate treatment or applying incorrect medical treatment, imposing unnecessary economic and physical burdens on the patient. Therefore, CEA and CA19-9 are often limited in use for the prognosis observation and treatment effect observation of patients already diagnosed with colorectal cancer (Non-Patent Document 1). According to a report, while the specificity of the CEA test is 99%, the sensitivity is only 12%, and the significance of tumor marker measurement as a colorectal cancer screening test is considered to be poor (Non-Patent Document 4).

[0015] Also, although still in the research stage, there are reports of discriminating colorectal cancer using the expression levels of microRNA (miRNA) in biological samples including blood, but none of them have reached practical application yet.

[0016] Patent Document 1 discloses a method for detecting colorectal cancer and other cancers using hsa-miR-92a-2-5p, hsa-miR-128-2-5p, and hsa-miR-24-3p in colorectal cancer tissues. However, this detection method requires obtaining tissue specimens of colorectal cancer by surgery, and this process places a heavy physical burden on patients, so it is not preferable as a detection method. In addition, this detection method lacks descriptions of the detection performance of colorectal cancer, such as specific accuracy, sensitivity, and specificity, so its industrial practicality is poor.

[0017] Patent Document 3 discloses a method for detecting colorectal cancer using multiple miRNAs such as hsa-miR-1231, hsa-miR-423-5p, and hsa-miR-1268a in colorectal tissues and feces. However, performing surgery to obtain colorectal cancer tissues places a heavy physical burden on patients, so it is not preferable as a detection method. In addition, although fecal specimens are non-invasively collected, there is a problem that the test substances may be unevenly present in feces, which easily causes variations in test results.

[0018] Patent Document 4 discloses a method for detecting colorectal cancer using hsa-miR-150-3p, miR-92a-2-5p, etc. in tissues, but there is no description of the detection performance such as accuracy, sensitivity, and specificity, and there is no description of a specific method for discriminating colorectal cancer using blood, so its industrial practicality is poor. Furthermore, since the above miRNA markers have not been verified in an independent specimen group, they lack reliability.

[0019] Thus, in the detection of colorectal cancer, the performance of existing tumor markers is low, or for markers in the research stage, the performance and detection methods are not specifically shown. Therefore, when using these markers, there is a possibility of unnecessary additional examinations due to misdetecting healthy individuals as colorectal cancer patients, or missing the opportunity for treatment due to overlooking colorectal cancer patients. In addition, measuring miRNAs consisting of dozens to hundreds increases the examination cost, so it is difficult to use for large-scale screening such as health check-ups. Also, collecting colorectal tissue to measure tumor markers is highly invasive to patients and not preferable. Therefore, a highly accurate colorectal cancer marker that can be detected from minimally invasive blood collection and can correctly distinguish colorectal cancer patients from colorectal cancer patients and healthy individuals from healthy individuals is required. Early detection and treatment of colorectal cancer can significantly improve the survival rate. Also, if colorectal cancer can be detected early, endoscopic surgery, which can be treated without laparotomy, becomes applicable. Therefore, a highly sensitive colorectal cancer marker that can detect even early-stage colorectal cancer is eagerly desired.

Means for Solving the Problems

[0020] As a result of intensive studies to solve the above problems, the present inventors have found a plurality of genes that can be used as detection markers for colorectal cancer from blood that can be collected with minimal invasion, and have found that colorectal cancer can be significantly detected by using a nucleic acid that can specifically bind thereto, thus completing the present invention.

[0021] <Summary of the Invention> That is, the present invention has the following features. (1) miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-204-3p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-3937, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p,miR-1227-5p, miR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085A kit for detecting colorectal cancer, comprising a nucleic acid that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-6752-5p and miR-135a-3p.

[0022] (2) miR-6726-5p is hsa-miR-6726-5p, and miR-42 57 is hsa-miR-4257, miR-6787-5p is hsa-miR-6 787-5p, miR-6780b-5p is hsa-miR-6780b-5p, miR-3131 is hsa-miR-3131, miR-7108-5p is hsa-miR-7108-5p, miR-1343-3p is hsa-miR-1 343-3p, miR-1247-3p is hsa-miR-1247-3p , miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-3679-5p is hsa-miR-367 9-5p, miR-7641 is hsa-miR-7641, miR-674 6-5p is hsa-miR-6746-5p, miR-8072 is hsa-miR-8072, miR-6741-5p is hsa-miR-6741-5p, miR-1908-5p is hsa-miR-1908-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4746-3p is hsa-miR-4746-3p, miR-744-5p is hsa-miR-744-5p, miR-4792 is hsa-miR-4792, miR-564 is hsa-miR-564, miR-6791-5p is hsa-miR-6791-5p , miR-6825-5p is hsa-miR-6825-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4665-3p is hsa-miR-4665-3p, miR-4467 is hsa-miR-4467, miR-3188 is hsa-miR-3188, miR-6125 is hsa-miR-6125, miR-6756-5p is hsa-miR-6756-5p, miR-1228-3p is hsa-miR-1228-3p, miR-8063 is hsa-miR-8063, miR-8069 is hsa-miR-8069, miR-6875-5p is hsa-miR-6875-5p, miR-3185 is hsa-miR-3185, miR-4433b-3p is hsa-miR-4433b-3p, miR-6887-5p is hsa-miR-6887-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-6724-5p is hsa-miR-6724-5p, miR-1914-3p is hsa-miR-1914-3p, miR-1225-5p is hsa-miR-1225-5p, miR-4419b is hsa-miR-4419b, miR-7110-5p is hsa-miR-7110-5p, miR-187-5p is hsa-miR-187-5p, miR-3184-5p is hsa-miR-3184-5p, miR-204-3p is hsa-miR-204-3p, miR-5572 is hsa-miR-5572, miR-6729-5p is hsa-miR-6729-5p, miR-615-5p is hsa-miR-615-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6515-3p is hsa-miR-6515-3p, miR-3937 is hsa-miR-3937, miR-6840-3p is hsa-miR-6840-3p, miR-6893-5p is hsa-miR-6893-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6717-5p is hsa-miR-6717-5p, miR-7113-3p is hsa-miR-7113-3p,miR-4665-5p is hsa-miR-4665-5p, miR-642b-3p is hsa-miR-642b-3p, miR-7109-5p is hsa-miR-7109-5p, miR-6842-5p is hsa-miR-6842-5p, miR-4442 is hsa-miR-4442, miR-4433-3p is hsa-miR-4433-3p, miR-4707-5p is hsa-miR-4707-5p, miR-6126 is hsa-miR-6126, miR-4449 is hsa-miR-4449, miR-4706 is hsa-miR-4706, miR-1913 is hsa-miR-1913, miR-602 is hsa-miR-602, miR-939-5p is hsa-miR-939-5p, miR-4695-5p is hsa-miR-4695-5p, miR-711 is hsa-miR-711, miR-6816-5p is hsa-miR-6816-5p, miR-4632-5p is hsa-miR-4632-5p, miR-6721-5p is hsa-miR-6721-5p, miR-7847-3p is hsa-miR-7847-3p, miR-6132 is hsa-miR-6132, miR-887-3p is hsa-miR-887-3p, miR-3679-3p is hsa-miR-3679-3p, miR-6784-5p is hsa-miR-6784-5p, miR-1249 is hsa-miR-1249, miR-937-5p is hsa-miR-937-5p, miR-5195-3p is hsa-miR-5195-3p, miR-6732-5p is hsa-miR-6732-5p, miR-4417 is hsa-miR-4417, miR-4281 is hsa-miR-4281, miR-4734 is hsa-miR-4734, miR-6766-3p is hsa-miR-6766-3p, miR-663a is hsa-miR-663a, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p, miR-1227-5p is hsa-miR-1227-5p,miR-6845-5p is hsa-miR-6845-5p, miR-6798-5p is hsa-miR-6798-5p, miR-3620-5p is hsa-miR-3620-5p, miR-1915-5p is hsa-miR-1915-5p, miR-4294 is hsa-miR-4294, miR-642a-3p is hsa-miR-642a-3p, miR-371a-5p is hsa-miR-371a-5p, miR-940 is hsa-miR-940, miR-4450 is hsa-miR-4450, miR-4723-5p is hsa-miR-4723-5p, miR-1469 is hsa-miR-1469, miR-6861-5p is hsa-miR-6861-5p, miR-7975 is hsa-miR-7975, miR-6879-5p is hsa-miR-6879-5p, miR-6802-5p is hsa-miR-6802-5p, miR-1268b is hsa-miR-1268b, miR-663b is hsa-miR-663b, miR-125a-3p is hsa-miR-125a-3p, miR-2861 is hsa-miR-2861, miR-6088 is hsa-miR-6088, miR-4758-5p is hsa-miR-4758-5p, miR-296-3p is hsa-miR-296-3p, miR-6738-5p is hsa-miR-6738-5p, miR-671-5p is hsa-miR-671-5p, miR-4454 is hsa-miR-4454, miR-4516 is hsa-miR-4516, miR-7845-5p is hsa-miR-7845-5p, miR-4741 is hsa-miR-4741, miR-92b-5p is hsa-miR-92b-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6805-3p is hsa-miR-6805-3p, miR-4725-3p is hsa-miR-4725-3p, miR-6782-5p is hsa-miR-6782-5p, miR-4688 is hsa-miR-4688, miR-6850-5p is hsa-miR-6850-5p,miR-6777-5p is hsa-miR-6777-5p, miR-6785-5p is hsa-miR-6785-5p, miR-7106-5p is hsa-miR-7106-5p, miR-3663-3p is hsa-miR-3663-3p, miR-6131 is hsa-miR-6131, miR-1915-3p is hsa-miR-1915-3p, miR-4532 is hsa-miR-4532, miR-6820-5p is hsa-miR-6820-5p, miR-4689 is hsa-miR-4689, miR-4638-5p is hsa-miR-4638-5p, miR-3656 is hsa-miR-3656, miR-3621 is hsa-miR-3621, miR-6769b-5p is hsa-miR-6769b-5p, miR-149-3p is hsa-miR-149-3p, miR-23b-3p is hsa-miR-23b-3p, miR-3135b is hsa-miR-3135b, miR-6848-5p is hsa-miR-6848-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-4327 is hsa-miR-4327, miR-6765-3p is hsa-miR-6765-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6877-5p is hsa-miR-6877-5p, miR-6727-5p is hsa-miR-6727-5p, miR-4534 is hsa-miR-4534, miR-614 is hsa-miR-614, miR-1202 is hsa-miR-1202, miR-575 is hsa-miR-575, miR-6870-5p is hsa-miR-6870-5p, miR-6722-3p is hsa-miR-6722-3p, miR-7977 is hsa-miR-7977, miR-4649-5p is hsa-miR-4649-5p, miR-4675 is hsa-miR-4675, miR-6075 is hsa-miR-6075, miR-6779-5p is hsa-miR-6779-5p, miR-4271 is hsa-miR-4271,miR-3196 is hsa-miR-3196, miR-6803-5p is hsa-miR-6803-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4648 is hsa-miR-4648, miR-4508 is hsa-miR-4508, miR-4749-5p is hsa-miR-4749-5p, miR-4505 is hsa-miR-4505, miR-5698 is hsa-miR-5698, miR-1199-5p is hsa-miR-1199-5p, miR-4763-3p is hsa-miR-4763-3p, miR-6836-3p is hsa-miR-6836-3p, miR-3195 is hsa-miR-3195, miR-718 is hsa-miR-718, miR-3178 is hsa-miR-3178, miR-638 is hsa-miR-638, miR-4497 is hsa-miR-4497, miR-6085 is hsa-miR-6085, miR-6752-5p is hsa-miR-6752-5p, and miR-135a-3p is hsa-miR-135a-3p, the kit according to (1).

[0023] (3) The nucleic acid is a polynucleotide represented by any of the following (a) to (e): (a) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, (c) A polynucleotide consisting of a base sequence complementary to a base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide comprising a base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a base sequence complementary to a base sequence in which u is t in the said base sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides of (a) to (d) above under stringent conditions, The kit according to (1) or (2), which is a polynucleotide selected from the group consisting of.

[0024] (4) The kit according to any of (1) to (3) above, further comprising a nucleic acid that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, and miR-24-3p, which are another colorectal cancer marker.

[0025] (5) The kit according to (4), wherein miR-1231 is hsa-miR-1231, miR-1233-5p is hsa-miR-1233-5p, miR-150-3p is hsa-miR-150-3p, miR-1225-3p is hsa-miR-1225-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-423-5p is hsa-miR-423-5p, miR-1268a is hsa-miR-1268a, miR-128-2-5p is hsa-miR-128-2-5p, and miR-24-3p is hsa-miR-24-3p.

[0026] (6) The said nucleic acid is a polynucleotide shown in the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the said base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (g) A polynucleotide comprising a base sequence represented by any of SEQ ID NOs: 172 to 180, (h) A polynucleotide comprising a base sequence represented by any of SEQ ID NOs: 172 to 180 or a base sequence complementary to a base sequence in which u is t in the said base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide comprising a base sequence represented by any of SEQ ID NOs: 172 to 180 or a base sequence complementary to a base sequence in which u is t in the said base sequence, and (j) A polynucleotide that hybridizes with a polynucleotide of any of the above (f) to (i) under stringent conditions, The kit according to (4) or (5), which is a polynucleotide selected from the group consisting of.

[0027] (7) The kit according to any of (1) to (6), further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, and miR-6090, which are another colorectal cancer marker.

[0028] (8) The kit according to (7), wherein miR-4697-5p is hsa-miR-4697-5p, miR-3197 is hsa-miR-3197, miR-675-5p is hsa-miR-675-5p, miR-4486 is hsa-miR-4486, miR-7107-5p is hsa-miR-7107-5p, miR-23a-3p is hsa-miR-23a-3p, miR-4667-5p is hsa-miR-4667-5p, miR-451a is hsa-miR-451a, miR-3940-5p is hsa-miR-3940-5p, miR-8059 is hsa-miR-8059, miR-6813-5p is hsa-miR-6813-5p, miR-4492 is hsa-miR-4492, miR-4476 is hsa-miR-4476, and miR-6090 is hsa-miR-6090.

[0029] (9) The nucleic acid is a polynucleotide represented by the following (k) to (o): (k) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (l) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 181 to 194, (m) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (n) A polynucleotide containing a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, and (o) A polynucleotide that hybridizes with any of the polynucleotides of (k) to (n) under stringent conditions. The kit according to (7) or (8), which is a polynucleotide selected from the group consisting of.

[0030] (10) The kit according to any one of (1) to (9), comprising at least two or more nucleic acids each of which can specifically bind to each of at least two or more polynucleotides selected from the group consisting of all the colorectal cancer markers described in (1) or (2).

[0031] (11) miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-204-3p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-3937, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p,miR-1227-5p, miR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085A device for detecting colorectal cancer, comprising a nucleic acid that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-6752-5p and miR-135a-3p.

[0032] (12) miR-6726-5p is hsa-miR-6726-5p, miR-4 257 is hsa-miR-4257, miR-6787-5p is hsa-miR-6787-5p, miR-6780b-5p is hsa-miR-6780b-5p, miR-3131 is hsa-miR-3131, miR-7108-5p is hsa-miR-7108-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1247-3p is hsa-miR-1247-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-3679-5p is hsa-miR-36 79-5p, miR-7641 is hsa-miR-7641, miR-67 46-5p is hsa-miR-6746-5p, miR-8072 is hsa-miR-8072, miR-6741-5p is hsa-miR-6741-5p ; miR-1908-5p is hsa-miR-1908-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4746-3p is hsa-miR-4746-3p, miR-744-5p is hsa-miR-744-5p, miR-4792 is hsa-miR-4792, miR-564 is hsa-miR-564, miR-6791-5p is hsa-miR-6791-5p, miR-6825-5p is hsa-miR-6825-5p, miR-682 6-5p is hsa-miR-6826-5p, miR-4665-3p is hsa-miR-4665-3p, miR-4467 is hsa-miR-4467, miR-3188 is hsa-miR-3188, miR-6125 is hsa-miR-6125, miR-6756-5p is hsa-miR-6756-5p , miR-1228-3p is hsa-miR-1228-3p, miR-8063 is hsa-miR-8063, miR-8069 is hsa-miR-8069, miR-6875-5p is hsa-miR-6875-5p, miR-318 5 is hsa-miR-3185, miR-4433b-3p is hsa-miR-4 433b-3p, miR-6887-5p is hsa-miR-6887-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-6 724-5p is hsa-miR-6724-5p, miR-1914-3p is hsa-miR-1914-3p, miR-1225-5p is hsa-miR-122 5-5p, miR-4419b is hsa-miR-4419b, miR-7 110-5p is hsa-miR-7110-5p, miR-187-5p is hsa-miR-187-5p, miR-3184-5p is hsa-miR-3184-5p, miR-204-3p is hsa-miR-204-3p, miR-5 572 is hsa-miR-5572, miR-6729-5p is hsa-miR-6729-5p, miR-615-5p is hsa-miR-615-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6515-3p is hsa-miR-6515-3p, miR-3937 is hsa-miR-3937, miR-6840-3p is hsa-miR-6840-3p, miR-6893-5p is hsa-miR-6893-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6717-5p is hsa-miR-6717-5p, miR-7113-3p is hsa-miR-7113-3p, miR-4665-5p is hsa-miR-4665-5p, miR-642b-3p is hsa-miR-642b-3p, miR-7109-5p is hsa-miR-7109-5p, miR-6842-5p is hsa-miR-6842-5p, miR-4442 is hsa-miR-4442, miR-4433-3p is hsa-miR-4433-3p, miR-4707-5p is hsa-miR-4707-5p, miR-6126 is hsa-miR-6126, miR-4449 is hsa-miR-4449, miR-4706 is hsa-miR-4706, miR-1913 is hsa-miR-1913, miR-602 is hsa-miR-602, miR-939-5p is hsa-miR-939-5p, miR-4695-5p is hsa-miR-4695-5p, miR-711 is hsa-miR-711, miR-6816-5p is hsa-miR-6816-5p, miR-4632-5p is hsa-miR-4632-5p, miR-6721-5p is hsa-miR-6721-5p, miR-7847-3p is hsa-miR-7847-3p, miR-6132 is hsa-miR-6132, miR-887-3p is hsa-miR-887-3p, miR-3679-3p is hsa-miR-3679-3p, miR-6784-5p is hsa-miR-6784-5p,miR-1249 is hsa-miR-1249, miR-937-5p is hsa-miR-937-5p, miR-5195-3p is hsa-miR-5195-3p, miR-6732-5p is hsa-miR-6732-5p, miR-4417 is hsa-miR-4417, miR-4281 is hsa-miR-4281, miR-4734 is hsa-miR-4734, miR-6766-3p is hsa-miR-6766-3p, miR-663a is hsa-miR-663a, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6845-5p is hsa-miR-6845-5p, miR-6798-5p is hsa-miR-6798-5p, miR-3620-5p is hsa-miR-3620-5p, miR-1915-5p is hsa-miR-1915-5p, miR-4294 is hsa-miR-4294, miR-642a-3p is hsa-miR-642a-3p, miR-371a-5p is hsa-miR-371a-5p, miR-940 is hsa-miR-940, miR-4450 is hsa-miR-4450, miR-4723-5p is hsa-miR-4723-5p, miR-1469 is hsa-miR-1469, miR-6861-5p is hsa-miR-6861-5p, miR-7975 is hsa-miR-7975, miR-6879-5p is hsa-miR-6879-5p, miR-6802-5p is hsa-miR-6802-5p, miR-1268b is hsa-miR-1268b, miR-663b is hsa-miR-663b, miR-125a-3p is hsa-miR-125a-3p, miR-2861 is hsa-miR-2861, miR-6088 is hsa-miR-6088, miR-4758-5p is hsa-miR-4758-5p, miR-296-3p is hsa-miR-296-3p, miR-6738-5p is hsa-miR-6738-5p,miR-671-5p is hsa-miR-671-5p, miR-4454 is hsa-miR-4454, miR-4516 is hsa-miR-4516, miR-7845-5p is hsa-miR-7845-5p, miR-4741 is hsa-miR-4741, miR-92b-5p is hsa-miR-92b-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6805-3p is hsa-miR-6805-3p, miR-4725-3p is hsa-miR-4725-3p, miR-6782-5p is hsa-miR-6782-5p, miR-4688 is hsa-miR-4688, miR-6850-5p is hsa-miR-6850-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6785-5p is hsa-miR-6785-5p, miR-7106-5p is hsa-miR-7106-5p, miR-3663-3p is hsa-miR-3663-3p, miR-6131 is hsa-miR-6131, miR-1915-3p is hsa-miR-1915-3p, miR-4532 is hsa-miR-4532, miR-6820-5p is hsa-miR-6820-5p, miR-4689 is hsa-miR-4689, miR-4638-5p is hsa-miR-4638-5p, miR-3656 is hsa-miR-3656, miR-3621 is hsa-miR-3621, miR-6769b-5p is hsa-miR-6769b-5p, miR-149-3p is hsa-miR-149-3p, miR-23b-3p is hsa-miR-23b-3p, miR-3135b is hsa-miR-3135b, miR-6848-5p is hsa-miR-6848-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-4327 is hsa-miR-4327, miR-6765-3p is hsa-miR-6765-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6877-5p is hsa-miR-6877-5p,miR-6727-5p is hsa-miR-6727-5p, miR-4534 is hsa-miR-4534, miR-614 is hsa-miR-614, miR-1202 is hsa-miR-1202, miR-575 is hsa-miR-575, miR-6870-5p is hsa-miR-6870-5p, miR-6722-3p is hsa-miR-6722-3p, miR-7977 is hsa-miR-7977, miR-4649-5p is hsa-miR-4649-5p, miR-4675 is hsa-miR-4675, miR-6075 is hsa-miR-6075, miR-6779-5p is hsa-miR-6779-5p, miR-4271 is hsa-miR-4271, miR-3196 is hsa-miR-3196, miR-6803-5p is hsa-miR-6803-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4648 is hsa-miR-4648, miR-4508 is hsa-miR-4508, miR-4749-5p is hsa-miR-4749-5p, miR-4505 is hsa-miR-4505, miR-5698 is hsa-miR-5698, miR-1199-5p is hsa-miR-1199-5p, miR-4763-3p is hsa-miR-4763-3p, miR-6836-3p is hsa-miR-6836-3p, miR-3195 is hsa-miR-3195, miR-718 is hsa-miR-718, miR-3178 is hsa-miR-3178, miR-638 is hsa-miR-638, miR-4497 is hsa-miR-4497, miR-6085 is hsa-miR-6085, miR-6752-5p is hsa-miR-6752-5p, and miR-135a-3p is hsa-miR-135a-3p, the device according to (11).

[0033] (13) The nucleic acid is a polynucleotide represented by the following (a) to (e): (a) A polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, (c) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the said nucleotide sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides of (a) to (d) under stringent conditions, The device according to (11) or (12), which is a polynucleotide selected from the group consisting of

[0034] (14) The device according to any of (11) to (13), further comprising a nucleic acid that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, and miR-24-3p, which are another colorectal cancer marker.

[0035] (15) The device according to (14), wherein miR-1231 is hsa-miR-1231, miR-1233-5p is hsa-miR-1233-5p, miR-150-3p is hsa-miR-150-3p, miR-1225-3p is hsa-miR-1225-3p, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-423-5p is hsa-miR-423-5p, miR-1268a is hsa-miR-1268a, miR-128-2-5p is hsa-miR-128-2-5p, and miR-24-3p is hsa-miR-24-3p.

[0036] (16) The nucleic acid is a polynucleotide represented by any of the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 172 to 180 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (g) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 172 to 180, (h) A polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 172 to 180 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 172 to 180 or a base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) to (i) under stringent conditions, The device according to (14) or (15), which is a polynucleotide selected from the group consisting of.

[0037] (17) The device according to any one of (11) to (16), further comprising a nucleic acid capable of specifically binding to at least one or more polynucleotides selected from the group consisting of miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, and miR-6090, which are another colorectal cancer marker.

[0038] (18) The device according to (17), wherein miR-4697-5p is hsa-miR-4697-5p, miR-3197 is hsa-miR-3197, miR-675-5p is hsa-miR-675-5p, miR-4486 is hsa-miR-4486, miR-7107-5p is hsa-miR-7107-5p, miR-23a-3p is hsa-miR-23a-3p, miR-4667-5p is hsa-miR-4667-5p, miR-451a is hsa-miR-451a, miR-3940-5p is hsa-miR-3940-5p, miR-8059 is hsa-miR-8059, miR-6813-5p is hsa-miR-6813-5p, miR-4492 is hsa-miR-4492, miR-4476 is hsa-miR-4476, and miR-6090 is hsa-miR-6090.

[0039] (19) The nucleic acid is a polynucleotide represented by any of the following (k) to (o): (k) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (l) A polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 181 to 194, (m) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 181 to 194 or a base sequence complementary to a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (n) A polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 181 to 194 or a base sequence complementary to a base sequence in which u is t in the base sequence, and (o) A polynucleotide that hybridizes with any one of the polynucleotides of (k) to (n) under stringent conditions, A polynucleotide selected from the group consisting of, the device according to (17) or (18).

[0040] (20) The device according to any one of (11) to (19), wherein the device is a device for measurement by hybridization technology.

[0041] (21) The device according to (20), wherein the hybridization technology is nucleic acid array technology.

[0042] (22) The device according to any one of (11) to (21), wherein the device contains at least two or more nucleic acids that can specifically bind to each of at least two or more polynucleotides selected from all the colorectal cancer markers described in (11) or (12).

[0043] (23) Measuring the expression level of a target nucleic acid in a specimen of a subject using the kit according to any one of (1) to (10) or the device according to any one of (11) to (22), and using the measured expression level and a control expression level of a healthy subject measured in the same manner to evaluate in vitro whether the subject has colorectal cancer or does not have colorectal cancer. A method for detecting colorectal cancer.

[0044] (24) The method according to (23), wherein the subject is a human.

[0045] (25) The method according to (23) or (24), wherein the sample is blood, serum or plasma.

[0046] <Definition of Terms> The terms used in this specification have the following definitions. The notations by abbreviations such as nucleotide, polynucleotide, DNA, and RNA shall follow the "Guidelines for the Preparation of Specifications etc. Containing Base Sequences or Amino Acid Sequences" (edited by the Japan Patent Office) and the common practice in the art.

[0047] As used herein, the term "polynucleotide" is used for nucleic acids including any of RNA, DNA, and RNA / DNA (chimeric). Note that the above DNA includes any of cDNA, genomic DNA, and synthetic DNA. Also, the above RNA includes any of total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA. As used herein, "synthetic DNA" and "synthetic RNA" refer to DNA and RNA artificially produced based on a predetermined base sequence (which may be either a natural sequence or a non-natural sequence), for example, using an automatic nucleic acid synthesizer. As used herein, the term "non-natural sequence" is intended to be used in a broad sense and includes sequences different from natural sequences, such as sequences containing substitutions, deletions, insertions, and / or additions of one or more nucleotides (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), and the like. Also, in this specification, polynucleotide is used interchangeably with nucleic acid.

[0048] As used herein, the term "fragment" is a polynucleotide having a base sequence of a continuous part of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, more preferably 19 bases or more.

[0049] As used herein, the term "gene" is intended to include not only RNA and double-stranded DNA, but also single-stranded DNA such as the positive strand (or sense strand) or complementary strand (or antisense strand) that constitutes them, and is not particularly limited by its length.

[0050] Accordingly, as used herein, unless otherwise specified, the term "gene" includes double-stranded DNA containing human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA having a sequence complementary to the positive strand (complementary strand), cDNA microRNA (miRNA), and fragments thereof, as well as transcripts. The "gene" is not limited to the "gene" represented by a specific base sequence (or SEQ ID NO.), but also includes "nucleic acids" encoding RNAs having biological functions equivalent to those of the RNAs encoded by these, such as homologs (i.e., homologs or orthologs), mutants such as gene polymorphisms, and derivatives. Specific examples of the "nucleic acid" encoding such a homolog, mutant, or derivative include a "nucleic acid" having a base sequence that hybridizes with the complementary sequence of the base sequence represented by any of SEQ ID NOs: 1 to 635 or a base sequence in which u is t in the base sequence under the stringent conditions described later. Note that the "gene" is not limited by the distinction of functional regions and can include, for example, an expression control region, a coding region, an exon, or an intron. Also, the "gene" may be contained in a cell, may exist alone outside the cell after being released, or may be encapsulated in vesicles called exosomes.

[0051] As used herein, "exosome" (also known as "exovesicle") is a vesicle enclosed by a lipid bilayer membrane secreted from a cell. Exosomes are derived from multivesicular endosomes and may contain biological substances such as "genes" such as RNA and DNA and proteins when released into the extracellular environment. Exosomes are known to be contained in body fluids such as blood, serum, plasma, and lymph.

[0052] As used herein, the term "transcript" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a site called a promoter upstream of the gene and synthesizes RNA by binding ribonucleotides to the 3' end so as to be complementary to the base sequence of the DNA. This RNA contains not only the gene itself, but also the entire sequence from the transcription start point to the end of the polyA sequence, including expression control regions, coding regions, exons or introns.

[0053] In addition, as used herein, "microRNA (miRNA)" refers, unless otherwise specified, to a non-coding RNA of 15 to 25 bases that is transcribed as an RNA precursor with a hairpin-like structure, cleaved by a dsRNA cleaving enzyme having RNase III cleavage activity, incorporated into a protein complex called RISC, and involved in the translational repression of mRNA. The term "miRNA" as used herein also includes not only "miRNA" represented by a specific base sequence (or SEQ ID NO), but also precursors (pre-miRNA, pri-miRNA) of said "miRNA", and miRNAs having biological functions equivalent thereto, such as homologs (i.e., homologs or orthologs), variants such as gene polymorphisms, and derivatives. Specific examples of such precursors, homologs, variants or derivatives include those that can be identified by miRBase release 20 (http: / / www.mirbase.org / ) and hybridize with the complementary sequence of any of the specific base sequences represented by SEQ ID NOs: 1 to 635 under the stringent conditions described below. Furthermore, the term "miRNA" as used herein may also be a gene product of an miR gene, and such a gene product includes mature miRNA (e.g., non-coding RNA of 15 to 25 bases, or 19 to 25 bases, involved in translational repression of mRNA as described above) or miRNA precursor (e.g., pre-miRNA or pri-miRNA as described above).

[0054] As used herein, "probe" includes a polynucleotide and / or a polynucleotide complementary thereto that is used to specifically detect RNA produced by gene expression or a polynucleotide derived therefrom.

[0055] As used herein, "primer" includes a polynucleotide and / or a polynucleotide complementary thereto that specifically recognizes and amplifies RNA produced by gene expression or a polynucleotide derived therefrom.

[0056] Here, the complementary polynucleotide (complementary strand, reverse strand) means a polynucleotide having a base-pair relationship such as A:T(U), G:C with respect to the full-length sequence or a partial sequence of a polynucleotide consisting of the base sequence defined by any of SEQ ID NOs: 1 to 635, or a base sequence in which u is t in the said base sequence (hereinafter referred to as the sense strand for convenience). However, such a complementary strand is not limited to the case where it forms a completely complementary sequence with the base sequence of the target sense strand, and may have a complementary relationship that can hybridize with the target sense strand under stringent conditions.

[0057] As used herein, "stringent conditions" refer to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater extent (for example, a measurement value of the average of the background measurement value + 2 times the standard error of the background measurement value) than to other sequences. Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization is performed. By controlling the stringency of hybridization and / or washing conditions, a target sequence that is 100% complementary to the nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.

[0058] As used herein, "Tm value" means the temperature at which the double-stranded portion of a polynucleotide denatures into single strands and the double strands and single strands are present in a ratio of 1:1.

[0059] As used herein, the term "variant" in the case of nucleic acids refers to natural variants resulting from polymorphisms, mutations, etc., or the nucleotide sequences of any of SEQ ID NOs: 1 to 194 and 606 to 614, or nucleotide sequences in which u is t in said nucleotide sequences, or variants including deletion, substitution, addition or insertion of one or more bases in partial sequences thereof, or variants showing about 90% or more, about 95% or more, about 97% or more, about 98% or more, about 99% or more sequence identity with each of said nucleotide sequences or partial sequences thereof, or nucleic acids that hybridize with polynucleotides or oligonucleotides containing said nucleotide sequences or partial sequences thereof under the stringent conditions defined above.

[0060] As used herein, the term "several" means an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.

[0061] As used herein, variants can be prepared using well-known techniques such as site-directed mutagenesis and mutagenesis methods using the PCR method.

[0062] As used herein, "% identity" can be determined using protein or gene search systems such as BLAST and FASTA described above, with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, p203 - 214; Altschul, S.F. et al., 1990, Journal of Molecular Biology, Vol. 215, p403 - 410; Pearson, W.R. et al., 1988, Proc. Natl. Acad. Sci. U.S.A., Vol. 85, p2444 - 2448).

[0063] As used herein, the term "derivative" refers to modified nucleic acids, including, but not limited to, labeled derivatives with fluorophores, etc., derivatives containing modified nucleotides (e.g., nucleotides containing groups such as alkyls like halogen and methyl, alkoxys like methoxy, thio, carboxymethyl, etc., and nucleotides that have undergone rearrangement of bases, saturation of double bonds, deamination, substitution of oxygen molecules with sulfur molecules, etc.), PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, Vol. 254, p1497 - 500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, p5401 - 5404), etc.

[0064] As used herein, the "nucleic acid" that can specifically bind to a polynucleotide selected from the above-mentioned miRNAs which are colorectal cancer markers is a synthetic or prepared nucleic acid, specifically including "nucleic acid probes" or "primers". In order to detect the presence or absence of colorectal cancer in a subject, or to diagnose the presence or absence of colorectal cancer, the degree of disease, the presence or absence and degree of improvement of colorectal cancer, the sensitivity to the treatment of colorectal cancer, or to screen for candidate substances useful for the prevention, improvement or treatment of colorectal cancer, it is used directly or indirectly. These include nucleotides, oligonucleotides and polynucleotides that can specifically recognize and bind to the transcripts represented by any of SEQ ID NOs: 1 - 635 or their cDNA synthetic nucleic acids in vivo, especially in specimens such as body fluids like blood and urine, which are related to the development of colorectal cancer. These nucleotides, oligonucleotides and polynucleotides can be effectively used as probes for detecting the above genes expressed in vivo, such as in tissues and cells, and as primers for amplifying the above genes expressed in vivo.

[0065] As used herein, "specifically bindable" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to other nucleic acids.

[0066] As used herein, the term "detection" can be replaced with the terms "examination", "measurement", "detection", or "decision support". Further, as used herein, the term "evaluation" is used in the sense of including assisting in diagnosis or evaluation based on examination results or measurement results.

[0067] As used herein, the term "subject" means mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep, and goats, and rodents such as mice and rats. Also, "healthy subject" also means such a mammal that is not affected by the cancer to be detected.

[0068] As used herein, "P" or "P-value" indicates the probability that a statistic more extreme than the statistic actually calculated from the data is observed under the null hypothesis in a statistical test. Therefore, the smaller the "P" or "P-value", the more a significant difference can be considered to exist between the comparison targets.

[0069] As used herein, "sensitivity" means the value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, it becomes possible to detect colorectal cancer at an early stage, leading to complete resection of the cancerous part and a reduction in the recurrence rate.

[0070] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). If the specificity is high, it prevents the unnecessary additional examinations due to misclassifying healthy subjects as colorectal cancer patients, leading to a reduction in the burden on patients and a reduction in medical costs.

[0071] As used herein, "accuracy" means the value of (number of true positives + number of true negatives) / (total number of cases). Accuracy indicates the proportion of correct discrimination results for all specimens and is the first index for evaluating the detection performance.

[0072] As used herein, the "specimen" to be determined, detected or diagnosed refers to tissues and biological materials in which the gene of the present invention exhibits changes in expression along with the occurrence, progression of colorectal cancer, and the exertion of therapeutic effects against colorectal cancer. Specifically, it refers to colorectal tissues and the surrounding blood vessels, lymph nodes and organs, as well as organs suspected of metastasis, skin, and body fluids such as blood, urine, saliva, sweat, tissue exudates, serum and plasma prepared from blood, feces, hair, and the like. Furthermore, it refers to biological samples extracted from these, specifically genes such as RNA and miRNA.

[0073] As used herein, the terms "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" include the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353) described in SEQ ID NO: 1, as well as homologs or orthologs of other species. The hsa-miR-6726-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6726-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 195).

[0074] As used herein, the terms "hsa-miR-4257 gene" or "hsa-miR-4257" include the hsa-miR-4257 gene (miRBase Accession No. MIMAT0016878) described in SEQ ID NO: 2, as well as homologs or orthologs of other species. The hsa-miR-4257 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4257" is known to have a hairpin-like structure as its precursor, "hsa-mir-4257" (miRBase Accession No. MI0015856, SEQ ID NO: 196).

[0075] As used herein, the term "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" includes the hsa-miR-6787-5p gene described in SEQ ID NO: 3 (miRBase Accession No. MIMAT0027474), as well as homologs or orthologs of other species. The hsa-miR-6787-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6787-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 197).

[0076] As used herein, the term "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" includes the hsa-miR-6780b-5p gene described in SEQ ID NO: 4 (miRBase Accession No. MIMAT0027572), as well as homologs or orthologs of other species. The hsa-miR-6780b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6780b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 198).

[0077] As used herein, the term "hsa-miR-3131 gene" or "hsa-miR-3131" includes the hsa-miR-3131 gene (miRBase Accession No. MIMAT0014996) set forth in SEQ ID NO: 5, as well as homologs or orthologs of other species. The hsa-miR-3131 gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3131" is known to have a hairpin-like structure as its precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, SEQ ID NO: 199).

[0078] As used herein, the term "hsa-miR-7108-5p gene" or "hsa-miR-7108-5p" includes the hsa-miR-7108-5p gene (miRBase Accession No. MIMAT0028113) set forth in SEQ ID NO: 6, as well as homologs or orthologs of other species. The hsa-miR-7108-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7108-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 200).

[0079] As used herein, the term "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" includes the hsa-miR-1343-3p gene described in SEQ ID NO: 7 (miRBase Accession No. MIMAT0019776), as well as homologs or orthologs of other species. The hsa-miR-1343-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-1343-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 201).

[0080] As used herein, the term "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" includes the hsa-miR-1247-3p gene described in SEQ ID NO: 8 (miRBase Accession No. MIMAT0022721), as well as homologs or orthologs of other species. The hsa-miR-1247-3p gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621. Also, "hsa-miR-1247-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1247" (miRBase Accession No. MI0006382, SEQ ID NO: 202).

[0081] As used herein, the term "hsa-miR-4651 gene" or "hsa-miR-4651" includes the hsa-miR-4651 gene described in SEQ ID NO: 9 (miRBase Accession No. MIMAT0019715), as well as homologs or orthologs of other species. The hsa-miR-4651 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4651" is known to have a hairpin-like structure as its precursor, "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 203).

[0082] As used herein, the term "hsa-miR-6757-5p gene" or "hsa-miR-6757-5p" includes the hsa-miR-6757-5p gene described in SEQ ID NO: 10 (miRBase Accession No. MIMAT0027414), as well as homologs or orthologs of other species. The hsa-miR-6757-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6757-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6757" (miRBase Accession No. MI0022602, SEQ ID NO: 204).

[0083] As used herein, the terms "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" include the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104) described in SEQ ID NO: 11, as well as homologs or orthologs of other species. The hsa-miR-3679-5p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637. Also, "hsa-miR-3679-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 205).

[0084] As used herein, the terms "hsa-miR-7641 gene" or "hsa-miR-7641" include the hsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) described in SEQ ID NO: 12, as well as homologs or orthologs of other species. The hsa-miR-7641 gene can be obtained by the method described in Yoo JK et al., 2013, Arch Pharm Res, 36, p353-358. Also, "hsa-miR-7641" is known to have hairpin-like structures as its precursors, "hsa-mir-7641-1" and "hsa-mir-7641-2" (miRBase Accession No. MI0024975, MI0024976, SEQ ID NO: 206, 207).

[0085] As used herein, the terms "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" include the hsa-miR-6746-5p gene (miRBase Accession No. MIMAT0027392) described in SEQ ID NO: 13, as well as homologs or orthologs of other species. The hsa-miR-6746-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6746-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 208).

[0086] As used herein, the terms "hsa-miR-8072 gene" or "hsa-miR-8072" include the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) described in SEQ ID NO: 14, as well as homologs or orthologs of other species. The hsa-miR-8072 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487. Also, "hsa-miR-8072" is known to have a hairpin-like structure as its precursor, "hsa-mir-8072" (miRBase Accession No. MI0025908, SEQ ID NO: 209).

[0087] As used herein, the term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" includes the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383) described in SEQ ID NO: 15, as well as homologs or orthologs of other species. The hsa-miR-6741-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6741-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 210).

[0088] As used herein, the term "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" includes the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881) described in SEQ ID NO: 16, as well as homologs or orthologs of other species. The hsa-miR-1908-5p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505. Also, "hsa-miR-1908-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 211).

[0089] As used herein, the term "hsa-miR-6857-5p gene" or "hsa-miR-6857-5p" includes the hsa-miR-6857-5p gene described in SEQ ID NO: 17 (miRBase Accession No. MIMAT0027614), as well as homologs or orthologs of other species. The hsa-miR-6857-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6857-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6857" (miRBase Accession No. MI0022703, SEQ ID NO: 212).

[0090] As used herein, the term "hsa-miR-4746-3p gene" or "hsa-miR-4746-3p" includes the hsa-miR-4746-3p gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0019881), as well as homologs or orthologs of other species. The hsa-miR-4746-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4746-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4746" (miRBase Accession No. MI0017385, SEQ ID NO: 213).

[0091] As used herein, the terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" include the hsa-miR-744-5p gene described in SEQ ID NO: 19 (miRBase Accession No. MIMAT0004945), as well as homologs or orthologs of other species. The hsa-miR-744-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-744-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 214).

[0092] As used herein, the terms "hsa-miR-4792 gene" or "hsa-miR-4792" include the hsa-miR-4792 gene described in SEQ ID NO: 20 (miRBase Accession No. MIMAT0019964), as well as homologs or orthologs of other species. The hsa-miR-4792 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4792" is known to have a hairpin-like structure as its precursor, "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 215).

[0093] As used herein, the term "hsa-miR-564 gene" or "hsa-miR-564" includes the hsa-miR-564 gene (miRBase Accession No. MIMAT0003228) described in SEQ ID NO: 21, as well as homologs or orthologs of other species. The hsa-miR-564 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-564" is known to have a precursor "hsa-mir-564" (miRBase Accession No. MI0003570, SEQ ID NO: 216) that forms a hairpin-like structure.

[0094] As used herein, the term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" includes the hsa-miR-6791-5p gene (miRBase Accession No. MIMAT0027482) described in SEQ ID NO: 22, as well as homologs or orthologs of other species. The hsa-miR-6791-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6791-5p" is known to have a precursor "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 217) that forms a hairpin-like structure.

[0095] As used herein, the term "hsa-miR-6825-5p gene" or "hsa-miR-6825-5p" includes the hsa-miR-6825-5p gene (miRBase Accession No. MIMAT0027550) described in SEQ ID NO: 23, as well as homologs or orthologs of other species. The hsa-miR-6825-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6825-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6825" (miRBase Accession No. MI0022670, SEQ ID NO: 218).

[0096] As used herein, the term "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" includes the hsa-miR-6826-5p gene (miRBase Accession No. MIMAT0027552) described in SEQ ID NO: 24, as well as homologs or orthologs of other species. The hsa-miR-6826-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6826-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 219).

[0097] As used herein, the term "hsa-miR-4665-3p gene" or "hsa-miR-4665-3p" includes the hsa-miR-4665-3p gene (miRBase Accession No. MIMAT0019740) described in SEQ ID NO: 25, as well as homologs or orthologs of other species. The hsa-miR-4665-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4665-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 220).

[0098] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" includes the hsa-miR-4467 gene (miRBase Accession No. MIMAT0018994) described in SEQ ID NO: 26, as well as homologs or orthologs of other species. The hsa-miR-4467 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4467" is known to have a hairpin-like structure as its precursor, "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 221).

[0099] As used herein, the terms "hsa-miR-3188 gene" or "hsa-miR-3188" include the hsa-miR-3188 gene described in SEQ ID NO: 27 (miRBase Accession No. MIMAT0015070), as well as homologs or orthologs of other species. The hsa-miR-3188 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3188" is known to have a hairpin-like structure as its precursor, "hsa-mir-3188" (miRBase Accession No. MI0014232, SEQ ID NO: 222).

[0100] As used herein, the terms "hsa-miR-6125 gene" or "hsa-miR-6125" include the hsa-miR-6125 gene described in SEQ ID NO: 28 (miRBase Accession No. MIMAT0024598), as well as homologs or orthologs of other species. The hsa-miR-6125 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287. Also, "hsa-miR-6125" is known to have a hairpin-like structure as its precursor, "hsa-mir-6125" (miRBase Accession No. MI0021259, SEQ ID NO: 223).

[0101] As used herein, the terms "hsa-miR-6756-5p gene" or "hsa-miR-6756-5p" include the hsa-miR-6756-5p gene described in SEQ ID NO: 29 (miRBase Accession No. MIMAT0027412), as well as homologs or orthologs of other species. The hsa-miR-6756-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6756-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6756" (miRBase Accession No. MI0022601, SEQ ID NO: 224).

[0102] As used herein, the terms "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" include the hsa-miR-1228-3p gene described in SEQ ID NO: 30 (miRBase Accession No. MIMAT0005583), as well as homologs or orthologs of other species. The hsa-miR-1228-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1228-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 225).

[0103] As used herein, the term "hsa-miR-8063 gene" or "hsa-miR-8063" includes the hsa-miR-8063 gene described in SEQ ID NO: 31 (miRBase Accession No. MIMAT0030990), as well as homologs or orthologs of other species. The hsa-miR-8063 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, p480-487. Also, "hsa-miR-8063" is known to have a hairpin-like structure as its precursor, "hsa-mir-8063" (miRBase Accession No. MI0025899, SEQ ID NO: 226).

[0104] As used herein, the term "hsa-miR-8069 gene" or "hsa-miR-8069" includes the hsa-miR-8069 gene described in SEQ ID NO: 32 (miRBase Accession No. MIMAT0030996), as well as homologs or orthologs of other species. The hsa-miR-8069 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, Vol. 39, p480-487. Also, "hsa-miR-8069" is known to have a hairpin-like structure as its precursor, "hsa-mir-8069" (miRBase Accession No. MI0025905, SEQ ID NO: 227).

[0105] As used herein, the terms "hsa-miR-6875-5p gene" or "hsa-miR-6875-5p" include the hsa-miR-6875-5p gene (miRBase Accession No. MIMAT0027650) described in SEQ ID NO: 33, as well as homologs or orthologs of other species. The hsa-miR-6875-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6875-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6875" (miRBase Accession No. MI0022722, SEQ ID NO: 228).

[0106] As used herein, the terms "hsa-miR-3185 gene" or "hsa-miR-3185" include the hsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) described in SEQ ID NO: 34, as well as homologs or orthologs of other species. The hsa-miR-3185 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3185" is known to have a hairpin-like structure as its precursor, "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 229).

[0107] As used herein, the term "hsa-miR-4433b-3p gene" or "hsa-miR-4433b-3p" includes the hsa-miR-4433b-3p gene (miRBase Accession No. MIMAT0030414) described in SEQ ID NO: 35, as well as homologs or orthologs of other species. The hsa-miR-4433b-3p gene can be obtained by the method described by Ple H et al., 2012, PLoS One, 7, e50746. Also, "hsa-miR-4433b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4433b" (miRBase Accession No. MI0025511, SEQ ID NO: 230).

[0108] As used herein, the term "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" includes the hsa-miR-6887-5p gene (miRBase Accession No. MIMAT0027674) described in SEQ ID NO: 36, as well as homologs or orthologs of other species. The hsa-miR-6887-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6887-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6887" (miRBase Accession No. MI0022734, SEQ ID NO: 231).

[0109] As used herein, the term "hsa-miR-128-1-5p gene" or "hsa-miR-128-1-5p" encompasses the hsa-miR-128-1-5p gene described in SEQ ID NO: 37 (miRBase Accession No. MIMAT0026477), as well as homologs or orthologs of other species. The hsa-miR-128-1-5p gene can be obtained by the method described by Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-128-1-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-1" (miRBase Accession No. MI0000447, SEQ ID NO: 232).

[0110] As used herein, the term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" encompasses the hsa-miR-6724-5p gene described in SEQ ID NO: 38 (miRBase Accession No. MIMAT0025856), as well as homologs or orthologs of other species. The hsa-miR-6724-5p gene can be obtained by the method described by Li Y et al., 2012, Gene, 497, p330-335. Also, "hsa-miR-6724-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6724" (miRBase Accession No. MI0022559, SEQ ID NO: 233).

[0111] As used herein, the term "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" encompasses the hsa-miR-1914-3p gene (miRBase Accession No. MIMAT0007890) described in SEQ ID NO: 39, as well as homologs or orthologs of other species. The hsa-miR-1914-3p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505. Also, "hsa-miR-1914-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 234).

[0112] As used herein, the term "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" encompasses the hsa-miR-1225-5p gene (miRBase Accession No. MIMAT0005572) described in SEQ ID NO: 40, as well as homologs or orthologs of other species. The hsa-miR-1225-5p gene can be obtained by the method described by Berezikov E et al., 2007, Mol Cell, Vol. 28, p328-336. Also, "hsa-miR-1225-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 235).

[0113] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" encompasses the hsa-miR-4419b gene described in SEQ ID NO: 41 (miRBase Accession No. MIMAT0019034), as well as homologs or orthologs of other species. The hsa-miR-4419b gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, pp. e118 - e127. Also, "hsa-miR-4419b" is known to have a hairpin-like structure as its precursor, "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 236).

[0114] As used herein, the term "hsa-miR-7110-5p gene" or "hsa-miR-7110-5p" encompasses the hsa-miR-7110-5p gene described in SEQ ID NO: 42 (miRBase Accession No. MIMAT0028117), as well as homologs or orthologs of other species. The hsa-miR-7110-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634 - 1645. Also, "hsa-miR-7110-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7110" (miRBase Accession No. MI0022961, SEQ ID NO: 237).

[0115] As used herein, the term "hsa-miR-187-5p gene" or "hsa-miR-187-5p" includes the hsa-miR-187-5p gene described in SEQ ID NO: 43 (miRBase Accession No. MIMAT0004561), as well as homologs or orthologs of other species. The hsa-miR-187-5p gene can be obtained by the method described by Lim LP et al., 2003, Science, Vol. 299, p1540. Also, "hsa-miR-187-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 238).

[0116] As used herein, the term "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" includes the hsa-miR-3184-5p gene described in SEQ ID NO: 44 (miRBase Accession No. MIMAT0015064), as well as homologs or orthologs of other species. The hsa-miR-3184-5p gene can be obtained by the method described by Stark MS et al., 2010, PLoS One, Vol. 5, e9685. Also, "hsa-miR-3184-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3184" (miRBase Accession No. MI0014226, SEQ ID NO: 239).

[0117] As used herein, the term "hsa-miR-204-3p gene" or "hsa-miR-204-3p" includes the hsa-miR-204-3p gene described in SEQ ID NO: 45 (miRBase Accession No. MIMAT0022693), as well as homologs or orthologs of other species. The hsa-miR-204-3p gene can be obtained by the method described by Lim LP et al. in Science, Vol. 299, p. 1540 in 2003. Also, "hsa-miR-204-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-204" (miRBase Accession No. MI0000284, SEQ ID NO: 240).

[0118] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" includes the hsa-miR-5572 gene described in SEQ ID NO: 46 (miRBase Accession No. MIMAT0022260), as well as homologs or orthologs of other species. The hsa-miR-5572 gene can be obtained by the method described by Tandon M et al. in Oral Dis, Vol. 18, pp. 127-131 in 2012. Also, "hsa-miR-5572" is known to have a hairpin-like structure as its precursor, "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 241).

[0119] As used herein, the term "hsa-miR-6729-5p gene" or "hsa-miR-6729-5p" includes the hsa-miR-6729-5p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0027359), as well as homologs or orthologs of other species. The hsa-miR-6729-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-6729-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6729" (miRBase Accession No. MI0022574, SEQ ID NO: 242).

[0120] As used herein, the term "hsa-miR-615-5p gene" or "hsa-miR-615-5p" includes the hsa-miR-615-5p gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0004804), as well as homologs or orthologs of other species. The hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103: p3687-3692. Also, "hsa-miR-615-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 243).

[0121] As used herein, the terms "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" include the hsa-miR-6749-5p gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0027398), as well as homologs or orthologs of other species. The hsa-miR-6749-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6749-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 244).

[0122] As used herein, the terms "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" include the hsa-miR-6515-3p gene described in SEQ ID NO: 50 (miRBase Accession No. MIMAT0025487), as well as homologs or orthologs of other species. The hsa-miR-6515-3p gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet, 20, p4025-4040. Also, "hsa-miR-6515-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 245).

[0123] As used herein, the terms "hsa-miR-3937 gene" or "hsa-miR-3937" include the hsa-miR-3937 gene described in SEQ ID NO: 51 (miRBase Accession No. MIMAT0018352), as well as homologs or orthologs of other species. The hsa-miR-3937 gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5, e10563. Also, "hsa-miR-3937" is known to have a hairpin-like structure as its precursor, "hsa-mir-3937" (miRBase Accession No. MI0016593, SEQ ID NO: 246).

[0124] As used herein, the terms "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" include the hsa-miR-6840-3p gene described in SEQ ID NO: 52 (miRBase Accession No. MIMAT0027583), as well as homologs or orthologs of other species. The hsa-miR-6840-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6840-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 247).

[0125] As used herein, the term "hsa-miR-6893-5p gene" or "hsa-miR-6893-5p" includes the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686) set forth in SEQ ID NO: 53, as well as homologs or orthologs of other species. The hsa-miR-6893-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-6893-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6893" (miRBase Accession No. MI0022740, SEQ ID NO: 248).

[0126] As used herein, the term "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" includes the hsa-miR-4728-5p gene (miRBase Accession No. MIMAT0019849) set forth in SEQ ID NO: 54, as well as homologs or orthologs of other species. The hsa-miR-4728-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71: p78-86. Also, "hsa-miR-4728-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 249).

[0127] As used herein, the term "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" includes the hsa-miR-6717-5p gene described in SEQ ID NO: 55 (miRBase Accession No. MIMAT0025846), as well as homologs or orthologs of other species. The hsa-miR-6717-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, p330-335. Also, "hsa-miR-6717-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 250).

[0128] As used herein, the term "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" includes the hsa-miR-7113-3p gene described in SEQ ID NO: 56 (miRBase Accession No. MIMAT0028124), as well as homologs or orthologs of other species. The hsa-miR-7113-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-7113-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7113" (miRBase Accession No. MI0022964, SEQ ID NO: 251).

[0129] As used herein, the term "hsa-miR-4665-5p gene" or "hsa-miR-4665-5p" includes the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739) described in SEQ ID NO: 57, as well as homologs or orthologs of other species. The hsa-miR-4665-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4665-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4665" (miRBase Accession No. MI0017295, SEQ ID NO: 220).

[0130] As used herein, the term "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" includes the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444) described in SEQ ID NO: 58, as well as homologs or orthologs of other species. The hsa-miR-642b-3p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-642b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642b" (miRBase Accession No. MI0016685, SEQ ID NO: 252).

[0131] As used herein, the term "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" encompasses the hsa-miR-7109-5p gene (miRBase Accession No. MIMAT0028115) described in SEQ ID NO: 59, as well as homologs or orthologs of other species. The hsa-miR-7109-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-7109-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7109" (miRBase Accession No. MI0022960, SEQ ID NO: 253).

[0132] As used herein, the term "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" encompasses the hsa-miR-6842-5p gene (miRBase Accession No. MIMAT0027586) described in SEQ ID NO: 60, as well as homologs or orthologs of other species. The hsa-miR-6842-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6842-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 254).

[0133] As used herein, the term "hsa-miR-4442 gene" or "hsa-miR-4442" encompasses the hsa-miR-4442 gene described in SEQ ID NO: 61 (miRBase Accession No. MIMAT0018960), as well as homologs or orthologs of other species. The hsa-miR-4442 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118 - e127. Also, "hsa-miR-4442" is known to have a hairpin-like structure as its precursor, "hsa-mir-4442" (miRBase Accession No. MI0016785, SEQ ID NO: 255).

[0134] As used herein, the term "hsa-miR-4433-3p gene" or "hsa-miR-4433-3p" encompasses the hsa-miR-4433-3p gene described in SEQ ID NO: 62 (miRBase Accession No. MIMAT0018949), as well as homologs or orthologs of other species. The hsa-miR-4433-3p gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118 - e127. Also, "hsa-miR-4433-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4433" (miRBase Accession No. MI0016773, SEQ ID NO: 256).

[0135] As used herein, the term "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" includes the hsa-miR-4707-5p gene (miRBase Accession No. MIMAT0019807) described in SEQ ID NO: 63, as well as homologs or orthologs of other species. The hsa-miR-4707-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4707-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 257).

[0136] As used herein, the term "hsa-miR-6126 gene" or "hsa-miR-6126" includes the hsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) described in SEQ ID NO: 64, as well as homologs or orthologs of other species. The hsa-miR-6126 gene can be obtained by the method described in Smith JL et al., 2012, J Virol, 86, p5278-5287. Also, "hsa-miR-6126" is known to have a hairpin-like structure as its precursor, "hsa-mir-6126" (miRBase Accession No. MI0021260, SEQ ID NO: 258).

[0137] As used herein, the term "hsa-miR-4449 gene" or "hsa-miR-4449" includes the hsa-miR-4449 gene (miRBase Accession No. MIMAT0018968) set forth in SEQ ID NO: 65, as well as homologs or orthologs of other species. The hsa-miR-4449 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4449" is known to have a hairpin-like structure as its precursor, "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 259).

[0138] As used herein, the term "hsa-miR-4706 gene" or "hsa-miR-4706" includes the hsa-miR-4706 gene (miRBase Accession No. MIMAT0019806) set forth in SEQ ID NO: 66, as well as homologs or orthologs of other species. The hsa-miR-4706 gene can be obtained by the method described by Persson H et al., 2011, Cancer Res, Vol. 71, p78-86. Also, "hsa-miR-4706" is known to have a hairpin-like structure as its precursor, "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 260).

[0139] As used herein, the term "hsa-miR-1913 gene" or "hsa-miR-1913" includes the hsa-miR-1913 gene described in SEQ ID NO: 67 (miRBase Accession No. MIMAT0007888), as well as homologs or orthologs of other species. The hsa-miR-1913 gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, p2496 - 2505. Also, "hsa-miR-1913" is known to have a hairpin-like structure as its precursor, "hsa-mir-1913" (miRBase Accession No. MI0008334, SEQ ID NO: 261).

[0140] As used herein, the term "hsa-miR-602 gene" or "hsa-miR-602" includes the hsa-miR-602 gene described in SEQ ID NO: 68 (miRBase Accession No. MIMAT0003270), as well as homologs or orthologs of other species. The hsa-miR-602 gene can be obtained by the method described by Cummins JM et al., 2006, Proc Natl Acad Sci U S A, Vol. 103, p3687 - 3692. Also, "hsa-miR-602" is known to have a hairpin-like structure as its precursor, "hsa-mir-602" (miRBase Accession No. MI0003615, SEQ ID NO: 262).

[0141] As used herein, the term "hsa-miR-939-5p gene" or "hsa-miR-939-5p" includes the hsa-miR-939-5p gene (miRBase Accession No. MIMAT0004982) described in SEQ ID NO: 69, as well as homologs or orthologs of other species. The hsa-miR-939-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, 67, p6031-6043. Also, "hsa-miR-939-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-939" (miRBase Accession No. MI0005761, SEQ ID NO: 263).

[0142] As used herein, the term "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" includes the hsa-miR-4695-5p gene (miRBase Accession No. MIMAT0019788) described in SEQ ID NO: 70, as well as homologs or orthologs of other species. The hsa-miR-4695-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4695-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 264).

[0143] As used herein, the terms "hsa-miR-711 gene" or "hsa-miR-711" include the hsa-miR-711 gene (miRBase Accession No. MIMAT0012734) described in SEQ ID NO: 71, as well as homologs or orthologs of other species. The hsa-miR-711 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, 9, p39. Also, "hsa-miR-711" is known to have a hairpin-like structure as its precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, SEQ ID NO: 265).

[0144] As used herein, the terms "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" include the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532) described in SEQ ID NO: 72, as well as homologs or orthologs of other species. The hsa-miR-6816-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6816-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 266).

[0145] As used herein, the term "hsa-miR-4632-5p gene" or "hsa-miR-4632-5p" includes the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977) described in SEQ ID NO: 73, as well as homologs or orthologs of other species. The hsa-miR-4632-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4632-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4632" (miRBase Accession No. MI0017259, SEQ ID NO: 267).

[0146] As used herein, the term "hsa-miR-6721-5p gene" or "hsa-miR-6721-5p" includes the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852) described in SEQ ID NO: 74, as well as homologs or orthologs of other species. The hsa-miR-6721-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, 497, p330-335. Also, "hsa-miR-6721-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6721" (miRBase Accession No. MI0022556, SEQ ID NO: 268).

[0147] As used herein, the terms "hsa-miR-7847-3p gene" or "hsa-miR-7847-3p" include the hsa-miR-7847-3p gene (miRBase Accession No. MIMAT0030422) described in SEQ ID NO: 75, as well as homologs or orthologs of other species. The hsa-miR-7847-3p gene can be obtained by the method described by Ple H et al., 2012, PLoS One, 7, e50746. Also, "hsa-miR-7847-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7847" (miRBase Accession No. MI0025517, SEQ ID NO: 269).

[0148] As used herein, the terms "hsa-miR-6132 gene" or "hsa-miR-6132" include the hsa-miR-6132 gene (miRBase Accession No. MIMAT0024616) described in SEQ ID NO: 76, as well as homologs or orthologs of other species. The hsa-miR-6132 gene can be obtained by the method described by Dannemann M et al., 2012, Genome Biol Evol, 4, p552-564. Also, "hsa-miR-6132" is known to have a hairpin-like structure as its precursor, "hsa-mir-6132" (miRBase Accession No. MI0021277, SEQ ID NO: 270).

[0149] As used herein, the term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" includes the hsa-miR-887-3p gene described in SEQ ID NO: 77 (miRBase Accession No. MIMAT0004951), as well as homologs or orthologs of other species. The hsa-miR-887-3p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-887-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 271).

[0150] As used herein, the term "hsa-miR-3679-3p gene" or "hsa-miR-3679-3p" includes the hsa-miR-3679-3p gene described in SEQ ID NO: 78 (miRBase Accession No. MIMAT0018105), as well as homologs or orthologs of other species. The hsa-miR-3679-3p gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One, 5, e9637. Also, "hsa-miR-3679-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 205).

[0151] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" includes the hsa-miR-6784-5p gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0027468), as well as homologs or orthologs of other species. The hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6784-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 272).

[0152] As used herein, the term "hsa-miR-1249 gene" or "hsa-miR-1249" includes the hsa-miR-1249 gene described in SEQ ID NO: 80 (miRBase Accession No. MIMAT0005901), as well as homologs or orthologs of other species. The hsa-miR-1249 gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18, p610-621. Also, "hsa-miR-1249" is known to have a hairpin-like structure as its precursor, "hsa-mir-1249" (miRBase Accession No. MI0006384, SEQ ID NO: 273).

[0153] As used herein, the term "hsa-miR-937-5p gene" or "hsa-miR-937-5p" includes the hsa-miR-937-5p gene described in SEQ ID NO: 81 (miRBase Accession No. MIMAT0022938), as well as homologs or orthologs of other species. The hsa-miR-937-5p gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, 67: p6031-6043. Also, "hsa-miR-937-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-937" (miRBase Accession No. MI0005759, SEQ ID NO: 274).

[0154] As used herein, the term "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" includes the hsa-miR-5195-3p gene described in SEQ ID NO: 82 (miRBase Accession No. MIMAT0021127), as well as homologs or orthologs of other species. The hsa-miR-5195-3p gene can be obtained by the method described in Schotte D et al., 2011, Leukemia, 25: p1389-1399. Also, "hsa-miR-5195-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 275).

[0155] As used herein, the term "hsa-miR-6732-5p gene" or "hsa-miR-6732-5p" encompasses the hsa-miR-6732-5p gene (miRBase Accession No. MIMAT0027365) described in SEQ ID NO: 83, as well as homologs or orthologs in other species. The hsa-miR-6732-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6732-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6732" (miRBase Accession No. MI0022577, SEQ ID NO: 276).

[0156] As used herein, the term "hsa-miR-4417 gene" or "hsa-miR-4417" encompasses the hsa-miR-4417 gene (miRBase Accession No. MIMAT0018929) described in SEQ ID NO: 84, as well as homologs or orthologs in other species. The hsa-miR-4417 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4417" is known to have a hairpin-like structure as its precursor, "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 277).

[0157] As used herein, the term "hsa-miR-4281 gene" or "hsa-miR-4281" encompasses the hsa-miR-4281 gene described in SEQ ID NO: 85 (miRBase Accession No. MIMAT0016907), as well as homologs or orthologs of other species. The hsa-miR-4281 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4281" is known to have a hairpin-like structure as its precursor, "hsa-mir-4281" (miRBase Accession No. MI0015885, SEQ ID NO: 278).

[0158] As used herein, the term "hsa-miR-4734 gene" or "hsa-miR-4734" encompasses the hsa-miR-4734 gene described in SEQ ID NO: 86 (miRBase Accession No. MIMAT0019859), as well as homologs or orthologs of other species. The hsa-miR-4734 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4734" is known to have a hairpin-like structure as its precursor, "hsa-mir-4734" (miRBase Accession No. MI0017371, SEQ ID NO: 279).

[0159] As used herein, the terms "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" include the hsa-miR-6766-3p gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0027433), as well as homologs or orthologs of other species. The hsa-miR-6766-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6766-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 280).

[0160] As used herein, the terms "hsa-miR-663a gene" or "hsa-miR-663a" include the hsa-miR-663a gene described in SEQ ID NO: 88 (miRBase Accession No. MIMAT0003326), as well as homologs or orthologs of other species. The hsa-miR-663a gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-663a" is known to have a hairpin-like structure as its precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 281).

[0161] As used herein, the term "hsa-miR-4513 gene" or "hsa-miR-4513" includes the hsa-miR-4513 gene (miRBase Accession No. MIMAT0019050) described in SEQ ID NO: 89, as well as homologs or orthologs of other species. The hsa-miR-4513 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4513" is known to have a hairpin-like structure as its precursor, "hsa-mir-4513" (miRBase Accession No. MI0016879, SEQ ID NO: 282).

[0162] As used herein, the term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" includes the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462) described in SEQ ID NO: 90, as well as homologs or orthologs of other species. The hsa-miR-6781-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6781-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 283).

[0163] As used herein, the term "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" includes the hsa-miR-1227-5p gene (miRBase Accession No. MIMAT0022941) described in SEQ ID NO: 91, as well as homologs or orthologs of other species. The hsa-miR-1227-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28: p328-336. Also, "hsa-miR-1227-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 284).

[0164] As used herein, the term "hsa-miR-6845-5p gene" or "hsa-miR-6845-5p" includes the hsa-miR-6845-5p gene (miRBase Accession No. MIMAT0027590) described in SEQ ID NO: 92, as well as homologs or orthologs of other species. The hsa-miR-6845-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-6845-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6845" (miRBase Accession No. MI0022691, SEQ ID NO: 285).

[0165] As used herein, the terms "hsa-miR-6798-5p gene" or "hsa-miR-6798-5p" include the hsa-miR-6798-5p gene described in SEQ ID NO: 93 (miRBase Accession No. MIMAT0027496), as well as homologs or orthologs of other species. The hsa-miR-6798-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6798-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6798" (miRBase Accession No. MI0022643, SEQ ID NO: 286).

[0166] As used herein, the terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" include the hsa-miR-3620-5p gene described in SEQ ID NO: 94 (miRBase Accession No. MIMAT0022967), as well as homologs or orthologs of other species. The hsa-miR-3620-5p gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-3620-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 287).

[0167] As used herein, the term "hsa-miR-1915-5p gene" or "hsa-miR-1915-5p" includes the hsa-miR-1915-5p gene described in SEQ ID NO: 95 (miRBase Accession No. MIMAT0007891), as well as homologs or orthologs of other species. The hsa-miR-1915-5p gene can be obtained by the method described by Bar M et al., 2008, Stem Cells, Vol. 26, p2496-2505. Also, "hsa-miR-1915-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 288).

[0168] As used herein, the term "hsa-miR-4294 gene" or "hsa-miR-4294" includes the hsa-miR-4294 gene described in SEQ ID NO: 96 (miRBase Accession No. MIMAT0016849), as well as homologs or orthologs of other species. The hsa-miR-4294 gene can be obtained by the method described by Goff LA et al., 2009, PLoS One, Vol. 4, e7192. Also, "hsa-miR-4294" is known to have a hairpin-like structure as its precursor, "hsa-mir-4294" (miRBase Accession No. MI0015827, SEQ ID NO: 289).

[0169] As used herein, the term "hsa-miR-642a-3p gene" or "hsa-miR-642a-3p" includes the hsa-miR-642a-3p gene described in SEQ ID NO: 97 (miRBase Accession No. MIMAT0020924), as well as homologs or orthologs of other species. The hsa-miR-642a-3p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-642a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-642a" (miRBase Accession No. MI0003657, SEQ ID NO: 290).

[0170] As used herein, the term "hsa-miR-371a-5p gene" or "hsa-miR-371a-5p" includes the hsa-miR-371a-5p gene described in SEQ ID NO: 98 (miRBase Accession No. MIMAT0004687), as well as homologs or orthologs of other species. The hsa-miR-371a-5p gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol, 270, p488-498. Also, "hsa-miR-371a-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-371a" (miRBase Accession No. MI0000779, SEQ ID NO: 291).

[0171] As used herein, the term "hsa-miR-940 gene" or "hsa-miR-940" encompasses the hsa-miR-940 gene described in SEQ ID NO: 99 (miRBase Accession No. MIMAT0004983), as well as homologs or orthologs of other species. The hsa-miR-940 gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res, 67, p6031-6043. Also, "hsa-miR-940" is known to have a hairpin-like structure as its precursor, "hsa-mir-940" (miRBase Accession No. MI0005762, SEQ ID NO: 292).

[0172] As used herein, the term "hsa-miR-4450 gene" or "hsa-miR-4450" encompasses the hsa-miR-4450 gene described in SEQ ID NO: 100 (miRBase Accession No. MIMAT0018971), as well as homologs or orthologs of other species. The hsa-miR-4450 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4450" is known to have a hairpin-like structure as its precursor, "hsa-mir-4450" (miRBase Accession No. MI0016795, SEQ ID NO: 293).

[0173] As used herein, the terms "hsa-miR-4723-5p gene" or "hsa-miR-4723-5p" include the hsa-miR-4723-5p gene described in SEQ ID NO: 101 (miRBase Accession No. MIMAT0019838), as well as homologs or orthologs of other species. The hsa-miR-4723-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4723-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4723" (miRBase Accession No. MI0017359, SEQ ID NO: 294).

[0174] As used herein, the terms "hsa-miR-1469 gene" or "hsa-miR-1469" include the hsa-miR-1469 gene described in SEQ ID NO: 102 (miRBase Accession No. MIMAT0007347), as well as homologs or orthologs of other species. The hsa-miR-1469 gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, 9, p157. Also, "hsa-miR-1469" is known to have a hairpin-like structure as its precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, SEQ ID NO: 295).

[0175] As used herein, the term "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" includes the hsa-miR-6861-5p gene (miRBase Accession No. MIMAT0027623) set forth in SEQ ID NO: 103, as well as homologs or orthologs of other species. The hsa-miR-6861-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-6861-5p" is known to have "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 296) which forms a hairpin-like structure as its precursor.

[0176] As used herein, the term "hsa-miR-7975 gene" or "hsa-miR-7975" includes the hsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) set forth in SEQ ID NO: 104, as well as homologs or orthologs of other species. The hsa-miR-7975 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. Also, "hsa-miR-7975" is known to have "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 297) which forms a hairpin-like structure as its precursor.

[0177] As used herein, the terms "hsa-miR-6879-5p gene" or "hsa-miR-6879-5p" include the hsa-miR-6879-5p gene (miRBase Accession No. MIMAT0027658) described in SEQ ID NO: 105, as well as homologs or orthologs of other species. The hsa-miR-6879-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6879-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6879" (miRBase Accession No. MI0022726, SEQ ID NO: 298).

[0178] As used herein, the terms "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" include the hsa-miR-6802-5p gene (miRBase Accession No. MIMAT0027504) described in SEQ ID NO: 106, as well as homologs or orthologs of other species. The hsa-miR-6802-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6802-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6802" (miRBase Accession No. MI0022647, SEQ ID NO: 299).

[0179] As used herein, the terms "hsa-miR-1268b gene" or "hsa-miR-1268b" include the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in SEQ ID NO: 107, as well as homologs or orthologs of other species. The hsa-miR-1268b gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-1268b" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 300).

[0180] As used herein, the terms "hsa-miR-663b gene" or "hsa-miR-663b" include the hsa-miR-663b gene (miRBase Accession No. MIMAT0005867) described in SEQ ID NO: 108, as well as homologs or orthologs of other species. The hsa-miR-663b gene can be obtained by the method described by Takada S et al., 2008, Leukemia, Vol. 22, pp. 1274-1278. Also, "hsa-miR-663b" is known to have a hairpin-like structure as its precursor, "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 301).

[0181] As used herein, the term "hsa-miR-125a-3p gene" or "hsa-miR-125a-3p" encompasses the hsa-miR-125a-3p gene described in SEQ ID NO: 109 (miRBase Accession No. MIMAT0004602), as well as homologs or orthologs of other species. The hsa-miR-125a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739. Also, "hsa-miR-125a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-125a" (miRBase Accession No. MI0000469, SEQ ID NO: 302).

[0182] As used herein, the term "hsa-miR-2861 gene" or "hsa-miR-2861" encompasses the hsa-miR-2861 gene described in SEQ ID NO: 110 (miRBase Accession No. MIMAT0013802), as well as homologs or orthologs of other species. The hsa-miR-2861 gene can be obtained by the method described in Li H et al., 2009, J Clin Invest, Vol. 119, p3666-3677. Also, "hsa-miR-2861" is known to have a hairpin-like structure as its precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 303).

[0183] As used herein, the terms "hsa-miR-6088 gene" or "hsa-miR-6088" include the hsa-miR-6088 gene (miRBase Accession No. MIMAT0023713) described in SEQ ID NO: 111, as well as homologs or orthologs of other species. The hsa-miR-6088 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, 21, p2049-2057. Also, "hsa-miR-6088" is known to have a hairpin-like structure as its precursor, "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 304).

[0184] As used herein, the terms "hsa-miR-4758-5p gene" or "hsa-miR-4758-5p" include the hsa-miR-4758-5p gene (miRBase Accession No. MIMAT0019903) described in SEQ ID NO: 112, as well as homologs or orthologs of other species. The hsa-miR-4758-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4758-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4758" (miRBase Accession No. MI0017399, SEQ ID NO: 305).

[0185] As used herein, the term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" includes the hsa-miR-296-3p gene (miRBase Accession No. MIMAT0004679) described in SEQ ID NO: 113, as well as homologs or orthologs of other species. The hsa-miR-296-3p gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell, Vol. 5, p351-358. Also, "hsa-miR-296-3p" is known to have a precursor "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 306) that forms a hairpin-like structure.

[0186] As used herein, the term "hsa-miR-6738-5p gene" or "hsa-miR-6738-5p" includes the hsa-miR-6738-5p gene (miRBase Accession No. MIMAT0027377) described in SEQ ID NO: 114, as well as homologs or orthologs of other species. The hsa-miR-6738-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-6738-5p" is known to have a precursor "hsa-mir-6738" (miRBase Accession No. MI0022583, SEQ ID NO: 307) that forms a hairpin-like structure.

[0187] As used herein, the term "hsa-miR-671-5p gene" or "hsa-miR-671-5p" includes the hsa-miR-671-5p gene described in SEQ ID NO: 115 (miRBase Accession No. MIMAT0003880), as well as homologs or orthologs of other species. The hsa-miR-671-5p gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res, 16, p1289-1298. Also, "hsa-miR-671-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-671" (miRBase Accession No. MI0003760, SEQ ID NO: 308).

[0188] As used herein, the term "hsa-miR-4454 gene" or "hsa-miR-4454" includes the hsa-miR-4454 gene described in SEQ ID NO: 116 (miRBase Accession No. MIMAT0018976), as well as homologs or orthologs of other species. The hsa-miR-4454 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4454" is known to have a hairpin-like structure as its precursor, "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 309).

[0189] As used herein, the terms "hsa-miR-4516 gene" or "hsa-miR-4516" include the hsa-miR-4516 gene (miRBase Accession No. MIMAT0019053) described in SEQ ID NO: 117, as well as homologs or orthologs of other species. The hsa-miR-4516 gene can be obtained by the method described by Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-4516" is known to have a hairpin-like structure as its precursor, "hsa-mir-4516" (miRBase Accession No. MI0016882, SEQ ID NO: 310).

[0190] As used herein, the terms "hsa-miR-7845-5p gene" or "hsa-miR-7845-5p" include the hsa-miR-7845-5p gene (miRBase Accession No. MIMAT0030420) described in SEQ ID NO: 118, as well as homologs or orthologs of other species. The hsa-miR-7845-5p gene can be obtained by the method described by Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also, "hsa-miR-7845-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7845" (miRBase Accession No. MI0025515, SEQ ID NO: 311).

[0191] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" includes the hsa-miR-4741 gene (miRBase Accession No. MIMAT0019871) described in SEQ ID NO: 119, as well as homologs or orthologs of other species. The hsa-miR-4741 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4741" is known to have a hairpin-like structure as its precursor, "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 312).

[0192] As used herein, the term "hsa-miR-92b-5p gene" or "hsa-miR-92b-5p" includes the hsa-miR-92b-5p gene (miRBase Accession No. MIMAT0004792) described in SEQ ID NO: 120, as well as homologs or orthologs of other species. The hsa-miR-92b-5p gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-92b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-92b" (miRBase Accession No. MI0003560, SEQ ID NO: 313).

[0193] As used herein, the terms "hsa-miR-6795-5p gene" or "hsa-miR-6795-5p" include the hsa-miR-6795-5p gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0027490), as well as homologs or orthologs of other species. The hsa-miR-6795-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6795-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6795" (miRBase Accession No. MI0022640, SEQ ID NO: 314).

[0194] As used herein, the terms "hsa-miR-6805-3p gene" or "hsa-miR-6805-3p" include the hsa-miR-6805-3p gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0027511), as well as homologs or orthologs of other species. The hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6805-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6805" (miRBase Accession No. MI0022650, SEQ ID NO: 315).

[0195] As used herein, the term "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" encompasses the hsa-miR-4725-3p gene described in SEQ ID NO: 123 (miRBase Accession No. MIMAT0019844), as well as homologs or orthologs in other species. The hsa-miR-4725-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, pp78 - 86. Also, "hsa-miR-4725-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 316).

[0196] As used herein, the term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" encompasses the hsa-miR-6782-5p gene described in SEQ ID NO: 124 (miRBase Accession No. MIMAT0027464), as well as homologs or orthologs in other species. The hsa-miR-6782-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, pp1634 - 1645. Also, "hsa-miR-6782-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 317).

[0197] As used herein, the term "hsa-miR-4688 gene" or "hsa-miR-4688" includes the hsa-miR-4688 gene described in SEQ ID NO: 125 (miRBase Accession No. MIMAT0019777), as well as homologs or orthologs of other species. The hsa-miR-4688 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4688" is known to have a hairpin-like structure as its precursor, "hsa-mir-4688" (miRBase Accession No. MI0017321, SEQ ID NO: 318).

[0198] As used herein, the term "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" includes the hsa-miR-6850-5p gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0027600), as well as homologs or orthologs of other species. The hsa-miR-6850-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6850-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 319).

[0199] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" includes the hsa-miR-6777-5p gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0027454), as well as homologs or orthologs of other species. The hsa-miR-6777-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6777-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 320).

[0200] As used herein, the term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" includes the hsa-miR-6785-5p gene described in SEQ ID NO: 128 (miRBase Accession No. MIMAT0027470), as well as homologs or orthologs of other species. The hsa-miR-6785-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6785-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 321).

[0201] As used herein, the terms "hsa-miR-7106-5p gene" or "hsa-miR-7106-5p" include the hsa-miR-7106-5p gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0028109), as well as homologs or orthologs in other species. The hsa-miR-7106-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-7106-5p" is known to have a precursor "hsa-mir-7106" (miRBase Accession No. MI0022957, SEQ ID NO: 322) that forms a hairpin-like structure.

[0202] As used herein, the terms "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" include the hsa-miR-3663-3p gene described in SEQ ID NO: 130 (miRBase Accession No. MIMAT0018085), as well as homologs or orthologs in other species. The hsa-miR-3663-3p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5: e10563. Also, "hsa-miR-3663-3p" is known to have a precursor "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 323) that forms a hairpin-like structure.

[0203] As used herein, the terms "hsa-miR-6131 gene" or "hsa-miR-6131" include the hsa-miR-6131 gene described in SEQ ID NO: 131 (miRBase Accession No. MIMAT0024615), as well as homologs or orthologs of other species. The hsa-miR-6131 gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol, 4, p552-564. Also, "hsa-miR-6131" is known to have a hairpin-like structure as its precursor, "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 324).

[0204] As used herein, the terms "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" include the hsa-miR-1915-3p gene described in SEQ ID NO: 132 (miRBase Accession No. MIMAT0007892), as well as homologs or orthologs of other species. The hsa-miR-1915-3p gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, 26, p2496-2505. Also, "hsa-miR-1915-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 288).

[0205] As used herein, the term "hsa-miR-4532 gene" or "hsa-miR-4532" includes the hsa-miR-4532 gene described in SEQ ID NO: 133 (miRBase Accession No. MIMAT0019071), as well as homologs or orthologs of other species. The hsa-miR-4532 gene can be obtained by the method described by Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4532" is known to have a hairpin-like structure as its precursor, "hsa-mir-4532" (miRBase Accession No. MI0016899, SEQ ID NO: 325).

[0206] As used herein, the term "hsa-miR-6820-5p gene" or "hsa-miR-6820-5p" includes the hsa-miR-6820-5p gene described in SEQ ID NO: 134 (miRBase Accession No. MIMAT0027540), as well as homologs or orthologs of other species. The hsa-miR-6820-5p gene can be obtained by the method described by Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6820-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6820" (miRBase Accession No. MI0022665, SEQ ID NO: 326).

[0207] As used herein, the terms "hsa-miR-4689 gene" or "hsa-miR-4689" include the hsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) described in SEQ ID NO: 135, as well as homologs or orthologs of other species. The hsa-miR-4689 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4689" is known to have a hairpin-like structure as its precursor, "hsa-mir-4689" (miRBase Accession No. MI0017322, SEQ ID NO: 327).

[0208] As used herein, the terms "hsa-miR-4638-5p gene" or "hsa-miR-4638-5p" include the hsa-miR-4638-5p gene (miRBase Accession No. MIMAT0019695) described in SEQ ID NO: 136, as well as homologs or orthologs of other species. The hsa-miR-4638-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4638-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4638" (miRBase Accession No. MI0017265, SEQ ID NO: 328).

[0209] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" includes the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in SEQ ID NO: 137, as well as homologs or orthologs of other species. The hsa-miR-3656 gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res, 38, p6234-6246. Also, "hsa-miR-3656" is known to have a hairpin-like structure as its precursor, "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 329).

[0210] As used herein, the term "hsa-miR-3621 gene" or "hsa-miR-3621" includes the hsa-miR-3621 gene (miRBase Accession No. MIMAT0018002) described in SEQ ID NO: 138, as well as homologs or orthologs of other species. The hsa-miR-3621 gene can be obtained by the method described in Witten D et al., 2010, BMC Biol, 8, p58. Also, "hsa-miR-3621" is known to have a hairpin-like structure as its precursor, "hsa-mir-3621" (miRBase Accession No. MI0016012, SEQ ID NO: 330).

[0211] As used herein, the term "hsa-miR-6769b-5p gene" or "hsa-miR-6769b-5p" includes the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620) described in SEQ ID NO: 139, as well as homologs or orthologs of other species. The hsa-miR-6769b-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6769b-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6769b" (miRBase Accession No. MI0022706, SEQ ID NO: 331).

[0212] As used herein, the term "hsa-miR-149-3p gene" or "hsa-miR-149-3p" includes the hsa-miR-149-3p gene (miRBase Accession No. MIMAT0004609) described in SEQ ID NO: 140, as well as homologs or orthologs of other species. The hsa-miR-149-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-149-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-149" (miRBase Accession No. MI0000478, SEQ ID NO: 332).

[0213] As used herein, the term "hsa-miR-23b-3p gene" or "hsa-miR-23b-3p" includes the hsa-miR-23b-3p gene described in SEQ ID NO: 141 (miRBase Accession No. MIMAT0000418), as well as homologs or orthologs of other species. The hsa-miR-23b-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-23b-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-23b" (miRBase Accession No. MI0000439, SEQ ID NO: 333).

[0214] As used herein, the term "hsa-miR-3135b gene" or "hsa-miR-3135b" includes the hsa-miR-3135b gene described in SEQ ID NO: 142 (miRBase Accession No. MIMAT0018985), as well as homologs or orthologs of other species. The hsa-miR-3135b gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-3135b" is known to have a hairpin-like structure as its precursor, "hsa-mir-3135b" (miRBase Accession No. MI0016809, SEQ ID NO: 334).

[0215] As used herein, the terms "hsa-miR-6848-5p gene" or "hsa-miR-6848-5p" include the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596) described in SEQ ID NO: 143, as well as homologs or orthologs of other species. The hsa-miR-6848-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6848-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6848" (miRBase Accession No. MI0022694, SEQ ID NO: 335).

[0216] As used herein, the terms "hsa-miR-6769a-5p gene" or "hsa-miR-6769a-5p" include the hsa-miR-6769a-5p gene (miRBase Accession No. MIMAT0027438) described in SEQ ID NO: 144, as well as homologs or orthologs of other species. The hsa-miR-6769a-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6769a-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6769a" (miRBase Accession No. MI0022614, SEQ ID NO: 336).

[0217] As used herein, the term "hsa-miR-4327 gene" or "hsa-miR-4327" includes the hsa-miR-4327 gene (miRBase Accession No. MIMAT0016889) described in SEQ ID NO: 145, as well as homologs or orthologs of other species. The hsa-miR-4327 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4327" is known to have a hairpin-like structure as its precursor, "hsa-mir-4327" (miRBase Accession No. MI0015867, SEQ ID NO: 337).

[0218] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" includes the hsa-miR-6765-3p gene (miRBase Accession No. MIMAT0027431) described in SEQ ID NO: 146, as well as homologs or orthologs of other species. The hsa-miR-6765-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6765-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 338).

[0219] As used herein, the term "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" includes the hsa-miR-6716-5p gene described in SEQ ID NO: 147 (miRBase Accession No. MIMAT0025844), as well as homologs or orthologs of other species. The hsa-miR-6716-5p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, pp. 330-335. Also, "hsa-miR-6716-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6716" (miRBase Accession No. MI0022550, SEQ ID NO: 339).

[0220] As used herein, the term "hsa-miR-6877-5p gene" or "hsa-miR-6877-5p" includes the hsa-miR-6877-5p gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0027654), as well as homologs or orthologs of other species. The hsa-miR-6877-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, pp. 1634-1645. Also, "hsa-miR-6877-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6877" (miRBase Accession No. MI0022724, SEQ ID NO: 340).

[0221] As used herein, the terms "hsa-miR-6727-5p gene" or "hsa-miR-6727-5p" include the hsa-miR-6727-5p gene (miRBase Accession No. MIMAT0027355) described in SEQ ID NO: 149, as well as homologs or orthologs of other species. The hsa-miR-6727-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6727-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6727" (miRBase Accession No. MI0022572, SEQ ID NO: 341).

[0222] As used herein, the terms "hsa-miR-4534 gene" or "hsa-miR-4534" include the hsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) described in SEQ ID NO: 150, as well as homologs or orthologs of other species. The hsa-miR-4534 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4534" is known to have a hairpin-like structure as its precursor, "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 342).

[0223] As used herein, the terms "hsa-miR-614 gene" or "hsa-miR-614" include the hsa-miR-614 gene (miRBase Accession No. MIMAT0003282) described in SEQ ID NO: 151, as well as homologs or orthologs of other species. The hsa-miR-614 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-614" is known to have a hairpin-like structure as its precursor, "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 343).

[0224] As used herein, the terms "hsa-miR-1202 gene" or "hsa-miR-1202" include the hsa-miR-1202 gene (miRBase Accession No. MIMAT0005865) described in SEQ ID NO: 152, as well as homologs or orthologs of other species. The hsa-miR-1202 gene can be obtained by the method described in Marton S et al., 2008, Leukemia, 22, p330-338. Also, "hsa-miR-1202" is known to have a hairpin-like structure as its precursor, "hsa-mir-1202" (miRBase Accession No. MI0006334, SEQ ID NO: 344).

[0225] As used herein, the terms "hsa-miR-575 gene" or "hsa-miR-575" include the hsa-miR-575 gene described in SEQ ID NO: 153 (miRBase Accession No. MIMAT0003240), as well as homologs or orthologs of other species. The hsa-miR-575 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-575" is known to have a hairpin-like structure as its precursor, "hsa-mir-575" (miRBase Accession No. MI0003582, SEQ ID NO: 345).

[0226] As used herein, the terms "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" include the hsa-miR-6870-5p gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0027640), as well as homologs or orthologs of other species. The hsa-miR-6870-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6870-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 346).

[0227] As used herein, the term "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" includes the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854) described in SEQ ID NO: 155, as well as homologs or orthologs of other species. The hsa-miR-6722-3p gene can be obtained by the method described in Li Y et al., 2012, Gene, Vol. 497, p330-335. Also, "hsa-miR-6722-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 347).

[0228] As used herein, the term "hsa-miR-7977 gene" or "hsa-miR-7977" includes the hsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) described in SEQ ID NO: 156, as well as homologs or orthologs of other species. The hsa-miR-7977 gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol, online edition. Also, "hsa-miR-7977" is known to have a hairpin-like structure as its precursor, "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 348).

[0229] As used herein, the term "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" includes the hsa-miR-4649-5p gene described in SEQ ID NO: 157 (miRBase Accession No. MIMAT0019711), as well as homologs or orthologs of other species. The hsa-miR-4649-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4649-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 349).

[0230] As used herein, the term "hsa-miR-4675 gene" or "hsa-miR-4675" includes the hsa-miR-4675 gene described in SEQ ID NO: 158 (miRBase Accession No. MIMAT0019757), as well as homologs or orthologs of other species. The hsa-miR-4675 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4675" is known to have a hairpin-like structure as its precursor, "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 350).

[0231] As used herein, the term "hsa-miR-6075 gene" or "hsa-miR-6075" includes the hsa-miR-6075 gene described in SEQ ID NO: 159 (miRBase Accession No. MIMAT0023700), as well as homologs or orthologs of other species. The hsa-miR-6075 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, Vol. 18, p472-484. Also, "hsa-miR-6075" is known to have a hairpin-like structure as its precursor, "hsa-mir-6075" (miRBase Accession No. MI0020352, SEQ ID NO: 351).

[0232] As used herein, the term "hsa-miR-6779-5p gene" or "hsa-miR-6779-5p" includes the hsa-miR-6779-5p gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0027458), as well as homologs or orthologs of other species. The hsa-miR-6779-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-6779-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6779" (miRBase Accession No. MI0022624, SEQ ID NO: 352).

[0233] As used herein, the term "hsa-miR-4271 gene" or "hsa-miR-4271" includes the hsa-miR-4271 gene described in SEQ ID NO: 161 (miRBase Accession No. MIMAT0016901), as well as homologs or orthologs of other species. The hsa-miR-4271 gene can be obtained by the method described in Goff LA et al., 2009, PLoS One, 4, e7192. Also, "hsa-miR-4271" is known to have a precursor "hsa-mir-4271" (miRBase Accession No. MI0015879, SEQ ID NO: 353) that forms a hairpin-like structure.

[0234] As used herein, the term "hsa-miR-3196 gene" or "hsa-miR-3196" includes the hsa-miR-3196 gene described in SEQ ID NO: 162 (miRBase Accession No. MIMAT0015080), as well as homologs or orthologs of other species. The hsa-miR-3196 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3196" is known to have a precursor "hsa-mir-3196" (miRBase Accession No. MI0014241, SEQ ID NO: 354) that forms a hairpin-like structure.

[0235] As used herein, the term "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" includes the hsa-miR-6803-5p gene (miRBase Accession No. MIMAT0027506) described in SEQ ID NO: 163, as well as homologs or orthologs of other species. The hsa-miR-6803-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6803-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6803" (miRBase Accession No. MI0022648, SEQ ID NO: 355).

[0236] As used herein, the term "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" includes the hsa-miR-6789-5p gene (miRBase Accession No. MIMAT0027478) described in SEQ ID NO: 164, as well as homologs or orthologs of other species. The hsa-miR-6789-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6789-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6789" (miRBase Accession No. MI0022634, SEQ ID NO: 356).

[0237] As used herein, the term "hsa-miR-4648 gene" or "hsa-miR-4648" includes the hsa-miR-4648 gene (miRBase Accession No. MIMAT0019710) described in SEQ ID NO: 165, as well as homologs or orthologs of other species. The hsa-miR-4648 gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4648" is known to have a hairpin-like structure as its precursor, "hsa-mir-4648" (miRBase Accession No. MI0017275, SEQ ID NO: 357).

[0238] As used herein, the term "hsa-miR-4508 gene" or "hsa-miR-4508" includes the hsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) described in SEQ ID NO: 166, as well as homologs or orthologs of other species. The hsa-miR-4508 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4508" is known to have a hairpin-like structure as its precursor, "hsa-mir-4508" (miRBase Accession No. MI0016872, SEQ ID NO: 358).

[0239] As used herein, the terms "hsa-miR-4749-5p gene" or "hsa-miR-4749-5p" include the hsa-miR-4749-5p gene described in SEQ ID NO: 167 (miRBase Accession No. MIMAT0019885), as well as homologs or orthologs of other species. The hsa-miR-4749-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4749-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4749" (miRBase Accession No. MI0017388, SEQ ID NO: 359).

[0240] As used herein, the terms "hsa-miR-4505 gene" or "hsa-miR-4505" include the hsa-miR-4505 gene described in SEQ ID NO: 168 (miRBase Accession No. MIMAT0019041), as well as homologs or orthologs of other species. The hsa-miR-4505 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4505" is known to have a hairpin-like structure as its precursor, "hsa-mir-4505" (miRBase Accession No. MI0016868, SEQ ID NO: 360).

[0241] As used herein, the terms "hsa-miR-5698 gene" or "hsa-miR-5698" include the hsa-miR-5698 gene described in SEQ ID NO: 169 (miRBase Accession No. MIMAT0022491), as well as homologs or orthologs of other species. The hsa-miR-5698 gene can be obtained by the method described in Watahiki A et al., 2011, PLoS One, 6, e24950. Also, "hsa-miR-5698" is known to have a hairpin-like structure as its precursor, "hsa-mir-5698" (miRBase Accession No. MI0019305, SEQ ID NO: 361).

[0242] As used herein, the terms "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" include the hsa-miR-1199-5p gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0031119), as well as homologs or orthologs of other species. The hsa-miR-1199-5p gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol, 42, p391-402. Also, "hsa-miR-1199-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1199" (miRBase Accession No. MI0020340, SEQ ID NO: 362).

[0243] As used herein, the term "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" includes the hsa-miR-4763-3p gene described in SEQ ID NO: 171 (miRBase Accession No. MIMAT0019913), as well as homologs or orthologs of other species. The hsa-miR-4763-3p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4763-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4763" (miRBase Accession No. MI0017404, SEQ ID NO: 363).

[0244] As used herein, the term "hsa-miR-1231 gene" or "hsa-miR-1231" includes the hsa-miR-1231 gene described in SEQ ID NO: 172 (miRBase Accession No. MIMAT0005586), as well as homologs or orthologs of other species. The hsa-miR-1231 gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1231" is known to have a hairpin-like structure as its precursor, "hsa-mir-1231" (miRBase Accession No. MI0006321, SEQ ID NO: 364).

[0245] As used herein, the terms "hsa-miR-1233-5p gene" or "hsa-miR-1233-5p" include the hsa-miR-1233-5p gene described in SEQ ID NO: 173 (miRBase Accession No. MIMAT0022943), as well as homologs or orthologs of other species. The hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336. Also, "hsa-miR-1233-5p" is known to have "hsa-mir-1233-1, hsa-mir-1233-2" (miRBase Accession No. MI0006323, MI0015973, SEQ ID NO: 365, 366) which form a hairpin-like structure as its precursor.

[0246] As used herein, the terms "hsa-miR-150-3p gene" or "hsa-miR-150-3p" include the hsa-miR-150-3p gene described in SEQ ID NO: 174 (miRBase Accession No. MIMAT0004610), as well as homologs or orthologs of other species. The hsa-miR-150-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, 12, p735-739. Also, "hsa-miR-150-3p" is known to have "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 367) which form a hairpin-like structure as its precursor.

[0247] As used herein, the terms "hsa-miR-1225-3p gene" or "hsa-miR-1225-3p" include the hsa-miR-1225-3p gene (miRBase Accession No. MIMAT0005573) described in SEQ ID NO: 175, as well as homologs or orthologs of other species. The hsa-miR-1225-3p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, Vol. 28, pp. 328-336. Also, "hsa-miR-1225-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 235).

[0248] As used herein, the terms "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" include the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508) described in SEQ ID NO: 176, as well as homologs or orthologs of other species. The hsa-miR-92a-2-5p gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, pp. 720-728. Also, "hsa-miR-92a-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 368).

[0249] As used herein, the terms "hsa-miR-423-5p gene" or "hsa-miR-423-5p" include the hsa-miR-423-5p gene (miRBase Accession No. MIMAT0004748) described in SEQ ID NO: 177, as well as homologs or orthologs of other species. The hsa-miR-423-5p gene can be obtained by the method described in Kasashima K et al., 2004, Biochem Biophys Res Commun, 322: p403-410. Also, "hsa-miR-423-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 369).

[0250] As used herein, the terms "hsa-miR-1268a gene" or "hsa-miR-1268a" include the hsa-miR-1268a gene (miRBase Accession No. MIMAT0005922) described in SEQ ID NO: 178, as well as homologs or orthologs of other species. The hsa-miR-1268a gene can be obtained by the method described in Morin RD et al., 2008, Genome Res, 18: p610-621. Also, "hsa-miR-1268a" is known to have a hairpin-like structure as its precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, SEQ ID NO: 370).

[0251] As used herein, the term "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" includes the hsa-miR-128-2-5p gene (miRBase Accession No. MIMAT0031095) described in SEQ ID NO: 179, as well as homologs or orthologs of other species. The hsa-miR-128-2-5p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739. Also, "hsa-miR-128-2-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 371).

[0252] As used herein, the term "hsa-miR-24-3p gene" or "hsa-miR-24-3p" includes the hsa-miR-24-3p gene (miRBase Accession No. MIMAT0000080) described in SEQ ID NO: 180, as well as homologs or orthologs of other species. The hsa-miR-24-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, Vol. 294, p853-858. Also, "hsa-miR-24-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-24-1, hsa-mir-24-2" (miRBase Accession No. MI0000080, MI0000081, SEQ ID NO: 372, 373).

[0253] As used herein, the term "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" includes the hsa-miR-4697-5p gene (miRBase Accession No. MIMAT0019791) described in SEQ ID NO: 181, as well as homologs or orthologs of other species. The hsa-miR-4697-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4697-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4697" (miRBase Accession No. MI0017330, SEQ ID NO: 374).

[0254] As used herein, the term "hsa-miR-3197 gene" or "hsa-miR-3197" includes the hsa-miR-3197 gene (miRBase Accession No. MIMAT0015082) described in SEQ ID NO: 182, as well as homologs or orthologs of other species. The hsa-miR-3197 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3197" is known to have a hairpin-like structure as its precursor, "hsa-mir-3197" (miRBase Accession No. MI0014245, SEQ ID NO: 375).

[0255] As used herein, the terms "hsa-miR-675-5p gene" or "hsa-miR-675-5p" include the hsa-miR-675-5p gene (miRBase Accession No. MIMAT0004284) described in SEQ ID NO: 183, as well as homologs or orthologs of other species. The hsa-miR-675-5p gene can be obtained by the method described in Cai X et al., 2007, RNA, Vol. 13, p313-316. Also, "hsa-miR-675-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-675" (miRBase Accession No. MI0005416, SEQ ID NO: 376).

[0256] As used herein, the terms "hsa-miR-4486 gene" or "hsa-miR-4486" include the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in SEQ ID NO: 184, as well as homologs or orthologs of other species. The hsa-miR-4486 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, e118-e127. Also, "hsa-miR-4486" is known to have a hairpin-like structure as its precursor, "hsa-mir-4486" (miRBase Accession No. MI0016847, SEQ ID NO: 377).

[0257] As used herein, the term "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" includes the hsa-miR-7107-5p gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0028111), as well as homologs or orthologs of other species. The hsa-miR-7107-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-7107-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 378).

[0258] As used herein, the term "hsa-miR-23a-3p gene" or "hsa-miR-23a-3p" includes the hsa-miR-23a-3p gene described in SEQ ID NO: 186 (miRBase Accession No. MIMAT0000078), as well as homologs or orthologs of other species. The hsa-miR-23a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science, 294: p853-858. Also, "hsa-miR-23a-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-23a" (miRBase Accession No. MI0000079, SEQ ID NO: 379).

[0259] As used herein, the term "hsa-miR-4667-5p gene" or "hsa-miR-4667-5p" encompasses the hsa-miR-4667-5p gene described in SEQ ID NO: 187 (miRBase Accession No. MIMAT0019743), as well as homologs or orthologs in other species. The hsa-miR-4667-5p gene can be obtained by the method described in Persson H et al., 2011, Cancer Res, 71, p78-86. Also, "hsa-miR-4667-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-4667" (miRBase Accession No. MI0017297, SEQ ID NO: 380).

[0260] As used herein, the term "hsa-miR-451a gene" or "hsa-miR-451a" encompasses the hsa-miR-451a gene described in SEQ ID NO: 188 (miRBase Accession No. MIMAT0001631), as well as homologs or orthologs in other species. The hsa-miR-451a gene can be obtained by the method described in Altuvia Y et al., 2005, Nucleic Acids Res, 33, p2697-2706. Also, "hsa-miR-451a" is known to have a hairpin-like structure as its precursor, "hsa-mir-451a" (miRBase Accession No. MI0001729, SEQ ID NO: 381).

[0261] As used herein, the term "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" includes the hsa-miR-3940-5p gene described in SEQ ID NO: 189 (miRBase Accession No. MIMAT0019229), as well as homologs or orthologs of other species. The hsa-miR-3940-5p gene can be obtained by the method described in Liao JY et al., 2010, PLoS One, 5, e10563. Also, "hsa-miR-3940-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-3940" (miRBase Accession No. MI0016597, SEQ ID NO: 382).

[0262] As used herein, the term "hsa-miR-8059 gene" or "hsa-miR-8059" includes the hsa-miR-8059 gene described in SEQ ID NO: 190 (miRBase Accession No. MIMAT0030986), as well as homologs or orthologs of other species. The hsa-miR-8059 gene can be obtained by the method described in Wang HJ et al., 2013, Shock, 39, p480-487. Also, "hsa-miR-8059" is known to have a hairpin-like structure as its precursor, "hsa-mir-8059" (miRBase Accession No. MI0025895, SEQ ID NO: 383).

[0263] As used herein, the terms "hsa-miR-6813-5p gene" or "hsa-miR-6813-5p" include the hsa-miR-6813-5p gene (miRBase Accession No. MIMAT0027526) described in SEQ ID NO: 191, as well as homologs or orthologs of other species. The hsa-miR-6813-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645. Also, "hsa-miR-6813-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6813" (miRBase Accession No. MI0022658, SEQ ID NO: 384).

[0264] As used herein, the terms "hsa-miR-4492 gene" or "hsa-miR-4492" include the hsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) described in SEQ ID NO: 192, as well as homologs or orthologs of other species. The hsa-miR-4492 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4492" is known to have a hairpin-like structure as its precursor, "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 385).

[0265] As used herein, the term "hsa-miR-4476 gene" or "hsa-miR-4476" includes the hsa-miR-4476 gene described in SEQ ID NO: 193 (miRBase Accession No. MIMAT0019003), as well as homologs or orthologs of other species. The hsa-miR-4476 gene can be obtained by the method described in Jima DD et al., 2010, Blood, Vol. 116, pp. e118-e127. Also, "hsa-miR-4476" is known to have a hairpin-like structure as its precursor, "hsa-mir-4476" (miRBase Accession No. MI0016828, SEQ ID NO: 386).

[0266] As used herein, the term "hsa-miR-6090 gene" or "hsa-miR-6090" includes the hsa-miR-6090 gene described in SEQ ID NO: 194 (miRBase Accession No. MIMAT0023715), as well as homologs or orthologs of other species. The hsa-miR-6090 gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev, Vol. 21, pp. 2049-2057. Also, "hsa-miR-6090" is known to have a hairpin-like structure as its precursor, "hsa-mir-6090" (miRBase Accession No. MI0020367, SEQ ID NO: 387).

[0267] As used herein, the terms "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" include the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575) described in SEQ ID NO: 606, as well as homologs or orthologs of other species. The hsa-miR-6836-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22: p1634-1645. Also, "hsa-miR-6836-3p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6836" (miRBase Accession No. MI0022682, SEQ ID NO: 615).

[0268] As used herein, the terms "hsa-miR-3195 gene" or "hsa-miR-3195" include the hsa-miR-3195 gene (miRBase Accession No. MIMAT0015079) described in SEQ ID NO: 607, as well as homologs or orthologs of other species. The hsa-miR-3195 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5: e9685. Also, "hsa-miR-3195" is known to have a hairpin-like structure as its precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, SEQ ID NO: 616).

[0269] As used herein, the terms "hsa-miR-718 gene" or "hsa-miR-718" include the hsa-miR-718 gene described in SEQ ID NO: 608 (miRBase Accession No. MIMAT0012735), as well as homologs or orthologs of other species. The hsa-miR-718 gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, 9, p39. Also, "hsa-miR-718" is known to have a hairpin-like structure as its precursor, "hsa-mir-718" (miRBase Accession No. MI0012489, SEQ ID NO: 617).

[0270] As used herein, the terms "hsa-miR-3178 gene" or "hsa-miR-3178" include the hsa-miR-3178 gene described in SEQ ID NO: 609 (miRBase Accession No. MIMAT0015055), as well as homologs or orthologs of other species. The hsa-miR-3178 gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, 5, e9685. Also, "hsa-miR-3178" is known to have a hairpin-like structure as its precursor, "hsa-mir-3178" (miRBase Accession No. MI0014212, SEQ ID NO: 618).

[0271] As used herein, the terms "hsa-miR-638 gene" or "hsa-miR-638" include the hsa-miR-638 gene described in SEQ ID NO: 610 (miRBase Accession No. MIMAT0003308), as well as homologs or orthologs of other species. The hsa-miR-638 gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A, 103, p3687-3692. Also, "hsa-miR-638" is known to have a hairpin-like structure as its precursor, "hsa-mir-638" (miRBase Accession No. MI0003653, SEQ ID NO: 619).

[0272] As used herein, the terms "hsa-miR-4497 gene" or "hsa-miR-4497" include the hsa-miR-4497 gene described in SEQ ID NO: 611 (miRBase Accession No. MIMAT0019032), as well as homologs or orthologs of other species. The hsa-miR-4497 gene can be obtained by the method described in Jima DD et al., 2010, Blood, 116, e118-e127. Also, "hsa-miR-4497" is known to have a hairpin-like structure as its precursor, "hsa-mir-4497" (miRBase Accession No. MI0016859, SEQ ID NO: 620).

[0273] As used herein, the terms "hsa-miR-6085 gene" or "hsa-miR-6085" include the hsa-miR-6085 gene described in SEQ ID NO: 612 (miRBase Accession No. MIMAT0023710), as well as homologs or orthologs in other species. The hsa-miR-6085 gene can be obtained by the method described in Voellenkle C et al., 2012, RNA, Vol. 18, p472-484. Also, "hsa-miR-6085" is known to have a hairpin-like structure as its precursor, "hsa-mir-6085" (miRBase Accession No. MI0020362, SEQ ID NO: 621).

[0274] As used herein, the terms "hsa-miR-6752-5p gene" or "hsa-miR-6752-5p" include the hsa-miR-6752-5p gene described in SEQ ID NO: 613 (miRBase Accession No. MIMAT0027404), as well as homologs or orthologs in other species. The hsa-miR-6752-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645. Also, "hsa-miR-6752-5p" is known to have a hairpin-like structure as its precursor, "hsa-mir-6752" (miRBase Accession No. MI0022597, SEQ ID NO: 622).

[0275] As used herein, the term "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" includes the hsa-miR-135a-3p gene described in SEQ ID NO: 614 (miRBase Accession No. MIMAT0004595), as well as homologs or orthologs of other species. The hsa-miR-135a-3p gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p735-739. Also, "hsa-miR-135a-3p" is known to have "hsa-mir-135a" (miRBase Accession No. MI0000452, SEQ ID NO: 623) which takes a hairpin-like structure as its precursor.

[0276] In addition, when mature miRNAs are excised from RNA precursors with a hairpin-like structure as mature miRNAs, one to several bases at the front and back of the sequence may be excised shorter or longer, or base substitutions may occur to form mutants, which are called isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, p. 610-621). In miRBase Release 20, in addition to the base sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614, mutants and fragments of base sequences represented by any of SEQ ID NOs: 388 to 605 and 624 to 635, which are called numerous isomiRs, are also shown. These mutants can also be obtained as miRNAs having the base sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614.That is, among the variants of the polynucleotide consisting of the nucleotide sequences represented by SEQ ID NOs: 5, 7, 8, 9, 11, 16, 19, 20, 21, 26, 27, 28, 30, 34, 37, 38, 39, 41, 43, 45, 46, 48, 50, 54, 55, 57, 58, 61, 62, 63, 64, 65, 66, 67, 69, 70, 71, 73, 74, 76, 77, 78, 80, 81, 82, 84, 85, 86, 88, 89, 94, 95, 97, 98, 99, 100, 101, 104, 107, 108, 109, 110, 111, 112, 113, 115, 116, 117, 119, 120, 123, 125, 131, 132, 133, 135, 136, 137, 140, 141, 142, 147, 151, 152, 157, 161, 162, 165, 166, 167, 168, 169, 171, 173, 174, 176, 177, 178, 179, 180, 182, 183, 184, 186, 187, 188, 189, 192, 193, 607, 608, 609, 610, 611 and 614, or the nucleotide sequences in which u is t in the said nucleotide sequences, for example, as the longest variant registered in miRBase Release 20, the polynucleotides represented by SEQ ID NOs: 388, 390, 392, 394, 396, 398, 400, 402, 404, 406, 408, 410, 412, 414, 416, 418, 420, 422, 424, 426, 428, 430, 432, 434, 436, 438, 440, 442, 444, 446, 448, 450, 452, 454, 456, 458, 460, 462, 464, 466, 468, 470, 472, 474, 476, 478, 480, 482, 484, 486, 488, 490, 492, 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, 624, 626, 628, 630, 632 and 634 are mentioned.In addition, among the variants of the polynucleotide consisting of the nucleotide sequences represented by SEQ ID NOs: 5, 7, 8, 9, 11, 16, 19, 20, 21, 26, 27, 28, 30, 34, 37, 38, 39, 41, 43, 45, 46, 48, 50, 54, 55, 57, 58, 61, 62, 63, 64, 65, 66, 67, 69, 70, 71, 73, 74, 76, 77, 78, 80, 81, 82, 84, 85, 86, 88, 89, 94, 95, 97, 98, 99, 100, 101, 104, 107, 108, 109, 110, 111, 112, 113, 115, 116, 117, 119, 120, 123, 125, 131, 132, 133, 135, 136, 137, 140, 141, 142, 147, 151, 152, 157, 161, 162, 165, 166, 167, 168, 169, 171, 173, 174, 176, 177, 178, 179, 180, 182, 183, 184, 186, 187, 188, 189, 192, 193, 607, 608, 609, 610, 611 and 614, or the nucleotide sequences in which u is t in the said nucleotide sequences, for example, as the shortest variants registered in miRBase Release 20, polynucleotides of the sequences represented by SEQ ID NOs: 389, 391, 393, 395, 397, 399, 401, 403, 405, 407, 409, 411, 413, 415, 417, 419, 421, 423, 425, 427, 429, 431, 433, 435, 437, 439, 441, 443, 445, 447, 449, 451, 453, 455, 457, 459, 461, 463, 465, 467, 469, 471, 473, 475, 477, 479, 481, 483, 485, 487, 489, 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, 591, 593, 595, 597, 599, 601, 603, 605, 625, 627, 629, 631, 633 and 635 may be mentioned.In addition to these variants and fragments, polynucleotides of numerous isomiRs registered in miRBase, with SEQ ID NOs: 1 to 194 and 606 to 614, are also included. Further, examples of polynucleotides containing the base sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 include polynucleotides represented by any of SEQ ID NOs: 195 to 387 and 615 to 623, which are their respective precursors.

[0277] The names of the genes represented by SEQ ID NOs: 1 to 635 and the miRBase Accession No. (registration number) are shown in Table 1.

[0278]

Table 1

Advantages of the Invention

[0279] According to the present invention, it has become possible to easily and highly accurately detect colorectal cancer.

[0280] For example, by using the measured values of the expression levels of several miRNAs in the blood, serum, and / or plasma of patients that can be obtained in a minimally invasive manner as an index, it is possible to easily detect whether a patient has colorectal cancer or not.

Brief Description of the Drawings

[0281]

Figure 1

Figure 2

Figure 3

Figure 4

Embodiments for Carrying Out the Invention

[0282] The present invention will be described in more detail below 1. Target Nucleic Acid for Colorectal Cancer Using the nucleic acid probe or primer for detecting colorectal cancer as defined above of the present invention, the main target nucleic acids as colorectal cancer markers for detecting the presence and / or absence of colorectal cancer or colorectal cancer cells include hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR-7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR-1908-5p, hsa-miR-6857-5p, hsa-miR-4746-3p, hsa-miR-744-5p, hsa-miR-4792, hsa-miR-564, hsa-miR-6791-5p, hsa-miR-6825-5p, hsa-miR-6826-5p, hsa-miR-4665-3p, hsa-miR-4467, hsa-miR-3188, hsa-miR-6125, hsa-miR-6756-5p, hsa-miR-1228-3p, hsa-miR-8063, hsa-miR-8069, hsa-miR-6875-5p, hsa-miR-3185, hsa-miR-4433b-3p, hsa-miR-6887-5p, hsa-miR-128-1-5p, hsa-miR-6724-5p, hsa-miR-1914-3p, hsa-miR-1225-5p, hsa-miR-4419b, hsa-miR-7110-5p, hsa-miR-187-5p, hsa-miR-3184-5p, hsa-miR-204-3p, hsa-miR-5572, hsa-miR-6729-5p, hsa-miR-615-5p, hsa-miR-6749-5p, hsa-miR-6515-3p, hsa-miR-3937, hsa-miR-6840-3p, hsa-miR-6893-5p, hsa-miR-4728-5p, hsa-miR-6717-5p, hsa-miR-7113-3p, hsa-miR-4665-5p, hsa-miR-642b-3p, hsa-miR-7109-5p, hsa-miR-6842-5p,hsa-miR-4442, hsa-miR-4433-3p, hsa-miR-4707-5p, hsa-miR-6126, hsa-miR-4449, hsa-miR-4706, hsa-miR-1913, hsa-miR-602, hsa-miR-939-5p, hsa-miR-4695-5p, hsa-miR-711, hsa-miR-6816-5p, hsa-miR-4632-5p, hsa-miR-6721-5p, hsa-miR-7847-3p, hsa-miR-6132, hsa-miR-887-3p, hsa-miR-3679-3p, hsa-miR-6784-5p, hsa-miR-1249, hsa-miR-937-5p, hsa-miR-5195-3p, hsa-miR-6732-5p, hsa-miR-4417, hsa-miR-4281, hsa-miR-4734, hsa-miR-6766-3p, hsa-miR-663a, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-1227-5p, hsa-miR-6845-5p, hsa-miR-6798-5p, hsa-miR-3620-5p, hsa-miR-1915-5p, hsa-miR-4294, hsa-miR-642a-3p, hsa-miR-371a-5p, hsa-miR-940, hsa-miR-4450, hsa-miR-4723-5p, hsa-miR-1469, hsa-miR-6861-5p, hsa-miR-7975, hsa-miR-6879-5p, hsa-miR-6802-5p, hsa-miR-1268b, hsa-miR-663b, hsa-miR-125a-3p, hsa-miR-2861, hsa-miR-6088, hsa-miR-4758-5p, hsa-miR-296-3p, hsa-miR-6738-5p, hsa-miR-671-5p, hsa-miR-4454, hsa-miR-4516, hsa-miR-7845-5p, hsa-miR-4741, hsa-miR-92b-5p, hsa-miR-6795-5p, hsa-miR-6805-3p, hsa-miR-4725-3p, hsa-miR-6782-5p, hsa-miR-4688, hsa-miR-6850-5p, hsa-miR-6777-5p, hsa-miR-6785-5pAt least one or more miRNAs selected from the group consisting of hsa-miR-7106-5p, hsa-miR-3663-3p, hsa-miR-6131, hsa-miR-1915-3p, hsa-miR-4532, hsa-miR-6820-5p, hsa-miR-4689, hsa-miR-4638-5p, hsa-miR-3656, hsa-miR-3621, hsa-miR-6769b-5p, hsa-miR-149-3p, hsa-miR-23b-3p, hsa-miR-3135b, hsa-miR-6848-5p, hsa-miR-6769a-5p, hsa-miR-4327, hsa-miR-6765-3p, hsa-miR-6716-5p, hsa-miR-6877-5p, hsa-miR-6727-5p, hsa-miR-4534, hsa-miR-614, hsa-miR-1202, hsa-miR-575, hsa-miR-6870-5p, hsa-miR-6722-3p, hsa-miR-7977, hsa-miR-4649-5p, hsa-miR-4675, hsa-miR-6075, hsa-miR-6779-5p, hsa-miR-4271, hsa-miR-3196, hsa-miR-6803-5p, hsa-miR-6789-5p, hsa-miR-4648, hsa-miR-4508, hsa-miR-4749-5p, hsa-miR-4505, hsa-miR-5698, hsa-miR-1199-5p, hsa-miR-4763-3p, hsa-miR-6836-3p, hsa-miR-3195, hsa-miR-718, hsa-miR-3178, hsa-miR-638, hsa-miR-4497, hsa-miR-6085, hsa-miR-6752-5p and hsa-miR-135a-3p can be used. Furthermore, other colorectal cancer markers that can be combined with these miRNAs, namely, hsa-miR-1231, hsa-miR-1233-5p, hsa-miR-150-3p, hsa-miR-1225-3p, hsa-miR-92a-2-5p, hsa-miR-423-5p, hsa-miR-1268a,At least one or more miRNAs selected from the group consisting of hsa-miR-128-2-5p and hsa-miR-24-3p can also be preferably used as target nucleic acids. Furthermore, other colorectal cancer markers that can be combined with these miRNAs, namely, at least one or more miRNAs selected from the group consisting of hsa-miR-4697-5p, hsa-miR-3197, hsa-miR-675-5p, hsa-miR-4486, hsa-miR-7107-5p, hsa-miR-23a-3p, hsa-miR-4667-5p, hsa-miR-451a, hsa-miR-3940-5p, hsa-miR-8059, hsa-miR-6813-5p, hsa-miR-4492, hsa-miR-4476, and hsa-miR-6090 can also be preferably used as target nucleic acids.

[0283] The above-mentioned miRNAs include, for example, human genes containing nucleotide sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 (i.e., hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR-7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR-1908-5p, hsa-miR-6857-5p, hsa-miR-4746-3p, hsa-miR-744-5p, hsa-miR-4792, hsa-miR-564, hsa-miR-6791-5p, hsa-miR-6825-5p, hsa-miR-6826-5p, hsa-miR-4665-3p, hsa-miR-4467, hsa-miR-3188, hsa-miR-6125, hsa-miR-6756-5p, hsa-miR-1228-3p, hsa-miR-8063, hsa-miR-8069, hsa-miR-6875-5p, hsa-miR-3185, hsa-miR-4433b-3p, hsa-miR-6887-5p, hsa-miR-128-1-5p, hsa-miR-6724-5p, hsa-miR-1914-3p, hsa-miR-1225-5p, hsa-miR-4419b, hsa-miR-7110-5p, hsa-miR-187-5p, hsa-miR-3184-5p, hsa-miR-204-3p, hsa-miR-5572, hsa-miR-6729-5p, hsa-miR-615-5p, hsa-miR-6749-5p, hsa-miR-6515-3p, hsa-miR-3937, hsa-miR-6840-3p, hsa-miR-6893-5p, hsa-miR-4728-5p, hsa-miR-6717-5p, hsa-miR-7113-3p, hsa-miR-4665-5p, hsa-miR-642b-3p, hsa-miR-7109-5p, hsa-miR-6842-5p, hsa-miR-4442,hsa-miR-4433-3p, hsa-miR-4707-5p, hsa-miR-6126, hsa-miR-4449, hsa-miR-4706, hsa-miR-1913, hsa-miR-602, hsa-miR-939-5p, hsa-miR-4695-5p, hsa-miR-711, hsa-miR-6816-5p, hsa-miR-4632-5p, hsa-miR-6721-5p, hsa-miR-7847-3p, hsa-miR-6132, hsa-miR-887-3p, hsa-miR-3679-3p, hsa-miR-6784-5p, hsa-miR-1249, hsa-miR-937-5p, hsa-miR-5195-3p, hsa-miR-6732-5p, hsa-miR-4417, hsa-miR-4281, hsa-miR-4734, hsa-miR-6766-3p, hsa-miR-663a, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-1227-5p, hsa-miR-6845-5p, hsa-miR-6798-5p, hsa-miR-3620-5p, hsa-miR-1915-5p, hsa-miR-4294, hsa-miR-642a-3p, hsa-miR-371a-5p, hsa-miR-940, hsa-miR-4450, hsa-miR-4723-5p, hsa-miR-1469, hsa-miR-6861-5p, hsa-miR-7975, hsa-miR-6879-5p, hsa-miR-6802-5p, hsa-miR-1268b, hsa-miR-663b, hsa-miR-125a-3p, hsa-miR-2861, hsa-miR-6088, hsa-miR-4758-5p, hsa-miR-296-3p, hsa-miR-6738-5p, hsa-miR-671-5p, hsa-miR-4454, hsa-miR-4516, hsa-miR-7845-5p, hsa-miR-4741, hsa-miR-92b-5p, hsa-miR-6795-5p, hsa-miR-6805-3p, hsa-miR-4725-3p, hsa-miR-6782-5p, hsa-miR-4688, hsa-miR-6850-5p, hsa-miR-6777-5p, hsa-miR-6785-5phsa-miR-7106-5p, hsa-miR-3663-3p, hsa-miR-6131, hsa-miR-1915-3p, hsa-miR-4532, hsa-miR-6820-5p, hsa-miR-4689, hsa-miR-4638-5p, hsa-miR-3656, hsa-miR-3621, hsa-miR-6769b-5p, hsa-miR-149-3p, hsa-miR-23b-3p, hsa-miR-3135b, hsa-miR-6848-5p, hsa-miR-6769a-5p, hsa-miR-4327, hsa-miR-6765-3p, hsa-miR-6716-5p, hsa-miR-6877-5p, hsa-miR-6727-5p, hsa-miR-4534, hsa-miR-614, hsa-miR-1202, hsa-miR-575, hsa-miR-6870-5p, hsa-miR-6722-3p, hsa-miR-7977, hsa-miR-4649-5p, hsa-miR-4675, hsa-miR-6075, hsa-miR-6779-5p, hsa-miR-4271, hsa-miR-3196, hsa-miR-6803-5p, hsa-miR-6789-5p, hsa-miR-4648, hsa-miR-4508, hsa-miR-4749-5p, hsa-miR-4505, hsa-miR-5698, hsa-miR-1199-5p, hsa-miR-4763-3p, hsa-miR-1231, hsa-miR-1233-5p, hsa-miR-150-3p, hsa-miR-1225-3p, hsa-miR-92a-2-5p, hsa-miR-423-5p, hsa-miR-1268a, hsa-miR-128-2-5p, hsa-miR-24-3p, hsa-miR-4697-5p, hsa-miR-3197, hsa-miR-675-5p, hsa-miR-4486, hsa-miR-7107-5p, hsa-miR-23a-3p, hsa-miR-4667-5p, hsa-miR-451a, hsa-miR-3940-5p, hsa-miR-8059, hsa-miR-6813-5p, hsa-miR-4492, hsa-miR-4476, hsa-miR-6090, hsa-miR-6836-3p, hsa-miR-3195hsa-miR-718, hsa-miR-3178, hsa-miR-638, hsa-miR-4497, hsa-miR-6085, hsa-miR-6752-5p, and hsa-miR-135a-3p), their homologs, their transcripts, and their variants or derivatives are included. Here, the gene, homolog, transcript, variant, and derivative are as defined above.,

[0284] Preferred target nucleic acids are human genes containing the nucleotide sequences represented by any of SEQ ID NOs: 1 to 635, or their transcripts, more preferably the transcripts, that is, miRNAs, their precursor RNAs, pri-miRNA or pre-miRNA.,

[0285] The first target gene is the hsa-miR-6726-5p gene, their homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.,

[0286] The second target gene is the hsa-miR-4257 gene, their homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.,

[0287] The third target gene is the hsa-miR-6787-5p gene, their homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.,

[0288] The fourth target gene is the hsa-miR-6780b-5p gene, their homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.,

[0289] The fifth target gene is the hsa-miR-3131 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0290] The sixth target gene is the hsa-miR-7108-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0291] The seventh target gene is the hsa-miR-1343-3p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0292] The eighth target gene is the hsa-miR-1247-3p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0293] The ninth target gene is the hsa-miR-4651 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0294] The tenth target gene is the hsa-miR-6757-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0295] The 11th target gene is the hsa-miR-3679-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0296] The 12th target gene is the hsa-miR-7641 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0297] The 13th target gene is the hsa-miR-6746-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0298] The 14th target gene is the hsa-miR-8072 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0299] The 15th target gene is the hsa-miR-6741-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0300] The 16th target gene is the hsa-miR-1908-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0301] The 17th target gene is the hsa-miR-6857-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0302] The 18th target gene is the hsa-miR-4746-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0303] The 19th target gene is the hsa-miR-744-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0304] The 20th target gene is the hsa-miR-4792 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0305] The 21st target gene is the hsa-miR-564 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0306] The 22nd target gene is the hsa-miR-6791-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0307] The 23rd target gene is the hsa-miR-6825-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0308] The 24th target gene is the hsa-miR-6826-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0309] The 25th target gene is the hsa-miR-4665-3p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0310] The 26th target gene is the hsa-miR-4467 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0311] The 27th target gene is the hsa-miR-3188 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0312] The 28th target gene is the hsa-miR-6125 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0313] The 29th target gene is the hsa-miR-6756-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0314] The 30th target gene is the hsa-miR-1228-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0315] The 31st target gene is the hsa-miR-8063 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0316] The 32nd target gene is the hsa-miR-8069 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0317] The 33rd target gene is the hsa-miR-6875-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0318] The 34th target gene is the hsa-miR-3185 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0319] The 35th target gene is the hsa-miR-4433b-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0320] The 36th target gene is the hsa-miR-6887-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0321] The 37th target gene is the hsa-miR-128-1-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0322] The 38th target gene is the hsa-miR-6724-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0323] The 39th target gene is the hsa-miR-1914-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0324] The 40th target gene is the hsa-miR-1225-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0325] The 41st target gene is the hsa-miR-4419b gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0326] The 42nd target gene is the hsa-miR-7110-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0327] The 43rd target gene is the hsa-miR-187-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0328] The 44th target gene is the hsa-miR-3184-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0329] The 45th target gene is the hsa-miR-204-3p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0330] The 46th target gene is the hsa-miR-5572 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0331] The 47th target gene is the hsa-miR-6729-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0332] The 48th target gene is the hsa-miR-615-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0333] The 49th target gene is the hsa-miR-6749-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0334] The 50th target gene is the hsa-miR-6515-3p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0335] The 51st target gene is the hsa-miR-3937 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0336] The 52nd target gene is the hsa-miR-6840-3p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0337] The 53rd target gene is the hsa-miR-6893-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0338] The 54th target gene is the hsa-miR-4728-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0339] The 55th target gene is the hsa-miR-6717-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0340] The 56th target gene is the hsa-miR-7113-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0341] The 57th target gene is the hsa-miR-4665-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0342] The 58th target gene is the hsa-miR-642b-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0343] The 59th target gene is the hsa-miR-7109-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0344] The 60th target gene is the hsa-miR-6842-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0345] The 61st target gene is the hsa-miR-4442 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0346] The 62nd target gene is the hsa-miR-4433-3p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0347] The 63rd target gene is the hsa-miR-4707-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0348] The 64th target gene is the hsa-miR-6126 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0349] The 65th target gene is the hsa-miR-4449 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0350] The 66th target gene is the hsa-miR-4706 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0351] The 67th target gene is the hsa-miR-1913 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0352] The 68th target gene is the hsa-miR-602 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0353] The 69th target gene is the hsa-miR-939-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0354] The 70th target gene is the hsa-miR-4695-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0355] The 71st target gene is the hsa-miR-711 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0356] The 72nd target gene is the hsa-miR-6816-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0357] The 73rd target gene is the hsa-miR-4632-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0358] The 74th target gene is the hsa-miR-6721-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0359] The 75th target gene is the hsa-miR-7847-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0360] The 76th target gene is the hsa-miR-6132 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0361] The 77th target gene is the hsa-miR-887-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0362] The 78th target gene is the hsa-miR-3679-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0363] The 79th target gene is the hsa-miR-6784-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0364] The 80th target gene is the hsa-miR-1249 gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0365] The 81st target gene is the hsa-miR-937-5p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0366] The 82nd target gene is the hsa-miR-5195-3p gene, its homologs, its transcripts, or its variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0367] The 83rd target gene is the hsa-miR-6732-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0368] The 84th target gene is the hsa-miR-4417 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0369] The 85th target gene is the hsa-miR-4281 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0370] The 86th target gene is the hsa-miR-4734 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0371] The 87th target gene is the hsa-miR-6766-3p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0372] The 88th target gene is the hsa-miR-663a gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0373] The 89th target gene is the hsa-miR-4513 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0374] The 90th target gene is the hsa-miR-6781-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0375] The 91st target gene is the hsa-miR-1227-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0376] The 92nd target gene is the hsa-miR-6845-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0377] The 93rd target gene is the hsa-miR-6798-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0378] The 94th target gene is the hsa-miR-3620-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0379] The 95th target gene is the hsa-miR-1915-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0380] The 96th target gene is the hsa-miR-4294 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0381] The 97th target gene is the hsa-miR-642a-3p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0382] The 98th target gene is the hsa-miR-371a-5p gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0383] The 99th target gene is the hsa-miR-940 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0384] The 100th target gene is the hsa-miR-4450 gene, its homologs, its transcripts, or its variants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0385] The 101st target gene is the hsa-miR-4723-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0386] The 102nd target gene is the hsa-miR-1469 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0387] The 103rd target gene is the hsa-miR-6861-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0388] The 104th target gene is the hsa-miR-7975 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0389] The 105th target gene is the hsa-miR-6879-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0390] The 106th target gene is the hsa-miR-6802-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0391] The 107th target gene is the hsa-miR-1268b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0392] The 108th target gene is the hsa-miR-663b gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0393] The 109th target gene is the hsa-miR-125a-3p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0394] The 110th target gene is the hsa-miR-2861 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0395] The 111th target gene is the hsa-miR-6088 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0396] The 112th target gene is the hsa-miR-4758-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0397] The target gene of No. 113 is the hsa-miR-296-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0398] The target gene of No. 114 is the hsa-miR-6738-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0399] The target gene of No. 115 is the hsa-miR-671-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0400] The target gene of No. 116 is the hsa-miR-4454 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0401] The target gene of No. 117 is the hsa-miR-4516 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0402] The target gene of No. 118 is the hsa-miR-7845-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0403] The 119th target gene is the hsa-miR-4741 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0404] The 120th target gene is the hsa-miR-92b-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0405] The 121st target gene is the hsa-miR-6795-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0406] The 122nd target gene is the hsa-miR-6805-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0407] The 123rd target gene is the hsa-miR-4725-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0408] The 124th target gene is the hsa-miR-6782-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0409] The 125th target gene is the hsa-miR-4688 gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0410] The 126th target gene is the hsa-miR-6850-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0411] The 127th target gene is the hsa-miR-6777-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0412] The 128th target gene is the hsa-miR-6785-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0413] The 129th target gene is the hsa-miR-7106-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0414] The 130th target gene is the hsa-miR-3663-3p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcripts can be a marker for colorectal cancer.

[0415] The 131st target gene is the hsa-miR-6131 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0416] The 132nd target gene is the hsa-miR-1915-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0417] The 133rd target gene is the hsa-miR-4532 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0418] The 134th target gene is the hsa-miR-6820-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0419] The 135th target gene is the hsa-miR-4689 gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0420] The 136th target gene is the hsa-miR-4638-5p gene, its homologs, their transcripts, or their mutants or derivatives. There has been no report so far that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0421] The 137th target gene is the hsa-miR-3656 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0422] The 138th target gene is the hsa-miR-3621 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0423] The 139th target gene is the hsa-miR-6769b-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0424] The 140th target gene is the hsa-miR-149-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0425] The 141st target gene is the hsa-miR-23b-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0426] The 142nd target gene is the hsa-miR-3135b gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0427] The 143rd target gene is the hsa-miR-6848-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0428] The 144th target gene is the hsa-miR-6769a-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0429] The 145th target gene is the hsa-miR-4327 gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0430] The 146th target gene is the hsa-miR-6765-3p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0431] The 147th target gene is the hsa-miR-6716-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0432] The 148th target gene is the hsa-miR-6877-5p gene, its homologs, their transcripts, or their variants or derivatives. There has been no report to date that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0433] The 149th target gene is the hsa-miR-6727-5p gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0434] The 150th target gene is the hsa-miR-4534 gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0435] The 151st target gene is the hsa-miR-614 gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0436] The 152nd target gene is the hsa-miR-1202 gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0437] The 153rd target gene is the hsa-miR-575 gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0438] The 154th target gene is the hsa-miR-6870-5p gene, its homologs, its transcripts, or its mutants or derivatives. To date, there has been no report that changes in the expression of this gene or its transcripts can serve as a marker for colorectal cancer.

[0439] The 155th target gene is the hsa-miR-6722-3p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0440] The 156th target gene is the hsa-miR-7977 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0441] The 157th target gene is the hsa-miR-4649-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0442] The 158th target gene is the hsa-miR-4675 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0443] The 159th target gene is the hsa-miR-6075 gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0444] The 160th target gene is the hsa-miR-6779-5p gene, its homologs, their transcripts, or their variants or derivatives. To date, there has been no report indicating that changes in the expression of this gene or its transcript can serve as a marker for colorectal cancer.

[0445] The 161st target gene is the hsa-miR-4271 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0446] The 162nd target gene is the hsa-miR-3196 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0447] The 163rd target gene is the hsa-miR-6803-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0448] The 164th target gene is the hsa-miR-6789-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0449] The 165th target gene is the hsa-miR-4648 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0450] The 166th target gene is the hsa-miR-4508 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0451] The 167th target gene is the hsa-miR-4749-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0452] The 168th target gene is the hsa-miR-4505 gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0453] The 169th target gene is the hsa-miR-5698 gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0454] The 170th target gene is the hsa-miR-1199-5p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0455] The 171st target gene is the hsa-miR-4763-3p gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0456] The 172nd target gene is the hsa-miR-1231 gene, its homologs, its transcripts, or its variants or derivatives. So far, there has been a report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer (Patent Document 3).

[0457] The 173rd target gene is the hsa-miR-1233-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Document 2).

[0458] The 174th target gene is the hsa-miR-150-3p gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Document 4).

[0459] The 175th target gene is the hsa-miR-1225-3p gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Document 2).

[0460] The 176th target gene is the hsa-miR-92a-2-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Documents 1 and 4).

[0461] The 177th target gene is the hsa-miR-423-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Document 3).

[0462] The 178th target gene is the hsa-miR-1268a gene, its homologs, their transcripts, or their variants or derivatives. So far, there have been reports that changes in the expression of this gene or its transcript can be markers for colorectal cancer (Patent Document 3).

[0463] The target gene of No. 179 is the hsa-miR-128-2-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, it has been reported that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer (Patent Document 1).

[0464] The target gene of No. 180 is the hsa-miR-24-3p gene, its homologs, their transcripts, or their variants or derivatives. So far, it has been reported that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer (Patent Document 1).

[0465] The target gene of No. 181 is the hsa-miR-4697-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer.

[0466] The target gene of No. 182 is the hsa-miR-3197 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer.

[0467] The target gene of No. 183 is the hsa-miR-675-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer.

[0468] The target gene of No. 184 is the hsa-miR-4486 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be used as a marker for colorectal cancer.

[0469] The 185th target gene is the hsa-miR-7107-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0470] The 186th target gene is the hsa-miR-23a-3p gene, its homologs, their transcripts, or their mutants or derivatives. There has been a report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer (Patent Document 2).

[0471] The 187th target gene is the hsa-miR-4667-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0472] The 188th target gene is the hsa-miR-451a gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0473] The 189th target gene is the hsa-miR-3940-5p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0474] The 190th target gene is the hsa-miR-8059 gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0475] The 191st target gene is the hsa-miR-6813-5p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0476] The 192nd target gene is the hsa-miR-4492 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0477] The 193rd target gene is the hsa-miR-4476 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0478] The 194th target gene is the hsa-miR-6090 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of this gene or its transcript can be a marker for colorectal cancer.

[0479] The 195th target gene is the hsa-miR-6836-3p gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0480] The 196th target gene is the hsa-miR-3195 gene, its homologs, their transcripts, or their variants or derivatives. So far, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0481] The 197th target gene is the hsa-miR-718 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0482] The 198th target gene is the hsa-miR-3178 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0483] The 199th target gene is the hsa-miR-638 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0484] The 200th target gene is the hsa-miR-4497 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0485] The 201st target gene is the hsa-miR-6085 gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0486] The 202nd target gene is the hsa-miR-6752-5p gene, its homologs, their transcripts, or their mutants or derivatives. To date, there has been no report that changes in the expression of the gene or its transcript can be a marker for colorectal cancer.

[0487] The target gene of No. 203 is the hsa-miR-135a-3p gene, its homologs, their transcripts, or their mutants or derivatives. So far, there has been no report that changes in the expression of a gene or its transcript can be a marker for colorectal cancer.

[0488] 2. Nucleic acid probe or primer for detecting colorectal cancer In the present invention, a nucleic acid capable of specifically binding to the target nucleic acid as the above colorectal cancer marker can be used as a nucleic acid for detecting or diagnosing colorectal cancer, for example, a nucleic acid probe or primer.

[0489] In the present invention, nucleic acid probes or primers that can be used for detecting or diagnosing colorectal cancer are the target nucleic acids as the above-mentioned colorectal cancer markers, such as hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR-7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR-1908-5p, hsa-miR-6857-5p, hsa-miR-4746-3p, hsa-miR-744-5p, hsa-miR-4792, hsa-miR-564, hsa-miR-6791-5p, hsa-miR-6825-5p, hsa-miR-6826-5p, hsa-miR-4665-3p, hsa-miR-4467, hsa-miR-3188, hsa-miR-6125, hsa-miR-6756-5p, hsa-miR-1228-3p, hsa-miR-8063, hsa-miR-8069, hsa-miR-6875-5p, hsa-miR-3185, hsa-miR-4433b-3p, hsa-miR-6887-5p, hsa-miR-128-1-5p, hsa-miR-6724-5p, hsa-miR-1914-3p, hsa-miR-1225-5p, hsa-miR-4419b, hsa-miR-7110-5p, hsa-miR-187-5p, hsa-miR-3184-5p, hsa-miR-204-3p, hsa-miR-5572, hsa-miR-6729-5p, hsa-miR-615-5p, hsa-miR-6749-5p, hsa-miR-6515-3p, hsa-miR-3937, hsa-miR-6840-3p, hsa-miR-6893-5p, hsa-miR-4728-5p, hsa-miR-6717-5p, hsa-miR-7113-3p, hsa-miR-4665-5p, hsa-miR-642b-3p, hsa-miR-7109-5p, hsa-miR-6842-5p, derived from humans.hsa-miR-4442, hsa-miR-4433-3p, hsa-miR-4707-5p, hsa-miR-6126, hsa-miR-4449, hsa-miR-4706, hsa-miR-1913, hsa-miR-602, hsa-miR-939-5p, hsa-miR-4695-5p, hsa-miR-711, hsa-miR-6816-5p, hsa-miR-4632-5p, hsa-miR-6721-5p, hsa-miR-7847-3p, hsa-miR-6132, hsa-miR-887-3p, hsa-miR-3679-3p, hsa-miR-6784-5p, hsa-miR-1249, hsa-miR-937-5p, hsa-miR-5195-3p, hsa-miR-6732-5p, hsa-miR-4417, hsa-miR-4281, hsa-miR-4734, hsa-miR-6766-3p, hsa-miR-663a, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-1227-5p, hsa-miR-6845-5p, hsa-miR-6798-5p, hsa-miR-3620-5p, hsa-miR-1915-5p, hsa-miR-4294, hsa-miR-642a-3p, hsa-miR-371a-5p, hsa-miR-940, hsa-miR-4450, hsa-miR-4723-5p, hsa-miR-1469, hsa-miR-6861-5p, hsa-miR-7975, hsa-miR-6879-5p, hsa-miR-6802-5p, hsa-miR-1268b, hsa-miR-663b, hsa-miR-125a-3p, hsa-miR-2861, hsa-miR-6088, hsa-miR-4758-5p, hsa-miR-296-3p, hsa-miR-6738-5p, hsa-miR-671-5p, hsa-miR-4454, hsa-miR-4516, hsa-miR-7845-5p, hsa-miR-4741, hsa-miR-92b-5p, hsa-miR-6795-5p, hsa-miR-6805-3p, hsa-miR-4725-3p, hsa-miR-6782-5p, hsa-miR-4688, hsa-miR-6850-5p, hsa-miR-6777-5p, hsa-miR-6785-5phsa-miR-7106-5p, hsa-miR-3663-3p, hsa-miR-6131, hsa-miR-1915-3p, hsa-miR-4532, hsa-miR-6820-5p, hsa-miR-4689, hsa-miR-4638-5p, hsa-miR-3656, hsa-miR-3621, hsa-miR-6769b-5p, hsa-miR-149-3p, hsa-miR-23b-3p, hsa-miR-3135b, hsa-miR-6848-5p, hsa-miR-6769a-5p, hsa-miR-4327, hsa-miR-6765-3p, hsa-miR-6716-5p, hsa-miR-6877-5p, hsa-miR-6727-5p, hsa-miR-4534, hsa-miR-614, hsa-miR-1202, hsa-miR-575, hsa-miR-6870-5p, hsa-miR-6722-3p, hsa-miR-7977, hsa-miR-4649-5p, hsa-miR-4675, hsa-miR-6075, hsa-miR-6779-5p, hsa-miR-4271, hsa-miR-3196, hsa-miR-6803-5p, hsa-miR-6789-5p, hsa-miR-4648, hsa-miR-4508, hsa-miR-4749-5p, hsa-miR-4505, hsa-miR-5698, hsa-miR-1199-5p, hsa-miR-4763-3p, hsa-miR-6836-3p, hsa-miR-3195, hsa-miR-718, hsa-miR-3178, hsa-miR-638, hsa-miR-4497, hsa-miR-6085, hsa-miR-6752-5p or hsa-miR-135a-3p or combinations thereof, or homologs thereof, their transcripts, their variants or derivatives, and hsa-miR-1231, hsa-miR-1233-5p, hsa-miR-150-3p, hsa-miR-1225-3p, hsa-miR-92a-2-5p, hsa-miR-423-5p, hsa-miR-1268a, hsa-miR-128-2-5p or hsa-miR-24-3p, or combinations thereof, or homologs thereof, their transcripts, which can optionally be combined with them,It enables qualitative and / or quantitative measurement of the presence, expression level or abundance of those variants or derivatives, and hsa-miR-4697-5p, hsa-miR-3197, hsa-miR-675-5p, hsa-miR-4486, hsa-miR-7107-5p, hsa-miR-23a-3p, hsa-miR-4667-5p, hsa-miR-451a, hsa-miR-3940-5p, hsa-miR-8059, hsa-miR-6813-5p, hsa-miR-4492, hsa-miR-4476 or hsa-miR-6090, or combinations thereof, or homologs thereof, their transcripts, their variants or derivatives, which can optionally be combined with them.

[0490] Compared with healthy subjects, for the target nucleic acids described above, in subjects suffering from colorectal cancer, the expression levels of some of them increase or some decrease depending on the type of the target nucleic acid (hereinafter referred to as "increase / decrease"). Therefore, the nucleic acids of the present invention can be effectively used for detecting colorectal cancer by measuring the expression levels of the above target nucleic acids in body fluids derived from subjects (such as humans) suspected of suffering from colorectal cancer and body fluids derived from healthy subjects and comparing them.

[0491] The nucleic acid probe or primer that can be used in the present invention is a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 171 and 606 to 614, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 1 to 171 and 606 to 614.

[0492] The nucleic acid probe or primer that can be used in the present invention can further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 172 to 180, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 172 to 180.

[0493] The nucleic acid probes or primers that can be used in the present invention may further include a nucleic acid probe that can specifically bind to a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 181 to 194, or a primer for amplifying a polynucleotide consisting of a base sequence represented by at least one of SEQ ID NOs: 181 to 194.

[0494] Specifically, the above-mentioned nucleic acid probes or primers include a polynucleotide group containing a base sequence represented by any one of SEQ ID NOs: 1 to 635, or a base sequence in which u is t in the base sequence, and its complementary polynucleotide group, and a polynucleotide group that hybridizes with DNA consisting of a base sequence complementary to the base sequence under stringent conditions (described later) and its complementary polynucleotide group, and one or a combination of a plurality of polynucleotides selected from a polynucleotide group containing 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 above-mentioned colorectal cancer marker, which is the target nucleic acid.

[0495] More specifically, examples of the nucleic acid probes or primers that can be used in the present invention are one or a plurality of polynucleotides selected from the group consisting of the following polynucleotides (a) to (e). (a) A polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a base sequence in which u is t in the base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a base sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, (c) A polynucleotide consisting of a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a base sequence in which u is t in the base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide comprising a nucleotide sequence complementary to the nucleotide sequence represented by any one of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the said nucleotide sequence, and (e) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d) above.

[0496] The nucleic acid probe or primer that can be used in the present invention may further contain, in addition to at least one or more polynucleotides selected from the above polynucleotides (a) to (e), a polynucleotide selected from the group consisting of the polynucleotides shown in the following (f) to (j). (f) A polynucleotide consisting of the nucleotide sequence represented by any one of SEQ ID NOs: 172 to 180 or a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (g) A polynucleotide containing the nucleotide sequence represented by any one of SEQ ID NOs: 172 to 180, (h) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by any one of SEQ ID NOs: 172 to 180 or a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by any one of SEQ ID NOs: 172 to 180 or a nucleotide sequence in which u is t in the said nucleotide sequence, and (j) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i) above.

[0497] The nucleic acid probe or primer that can be used in the present invention may further contain, in addition to at least one or more polynucleotides selected from the above polynucleotides (a) to (j), a polynucleotide selected from the group consisting of the polynucleotides shown in the following (k) to (o). (k) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (l) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 181 to 194, (m) a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, or a base sequence complementary thereto, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (n) A polynucleotide containing a base sequence complementary to a base sequence represented by any of SEQ ID NOs: 181 to 194 or a base sequence in which u is t in the base sequence, and (o) A polynucleotide that hybridizes with any of the polynucleotides of (k) to (n) under stringent conditions.

[0498] In the above polynucleotides, "a fragment thereof containing 15 or more consecutive bases" can include, but is not limited to, for example, the number of bases in the range of 15 consecutive bases to less than the total number of bases in the sequence, 17 consecutive bases to less than the total number of bases in the sequence, 19 consecutive bases to less than the total number of bases in the sequence, etc. in the base sequence of each polynucleotide.

[0499] Any of the above polynucleotides or fragments thereof used in the present invention may be DNA or RNA.

[0500] The above polynucleotides that can be used in the present invention can be prepared using general techniques such as DNA recombination techniques, PCR methods, and methods using DNA / RNA automatic synthesizers.

[0501] DNA recombination technology and PCR methods can use techniques described, for example, in Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).

[0502] Human-derived hsa-miR-6726-5p, hsa-miR-4257, hsa-miR-6787-5p, hsa-miR-6780b-5p, hsa-miR-3131, hsa-miR-7108-5p, hsa-miR-1343-3p, hsa-miR-1247-3p, hsa-miR-4651, hsa-miR-6757-5p, hsa-miR-3679-5p, hsa-miR-7641, hsa-miR-6746-5p, hsa-miR-8072, hsa-miR-6741-5p, hsa-miR-1908-5p, hsa-miR-6857-5p, hsa-miR-4746-3p, hsa-miR-744-5p, hsa-miR-4792, hsa-miR-564, hsa-miR-6791-5p, hsa-miR-6825-5p, hsa-miR-6826-5p, hsa-miR-4665-3p, hsa-miR-4467, hsa-miR-3188, hsa-miR-6125, hsa-miR-6756-5p, hsa-miR-1228-3p, hsa-miR-8063, hsa-miR-8069, hsa-miR-6875-5p, hsa-miR-3185, hsa-miR-4433b-3p, hsa-miR-6887-5p, hsa-miR-128-1-5p, hsa-miR-6724-5p, hsa-miR-1914-3p, hsa-miR-1225-5p, hsa-miR-4419b, hsa-miR-7110-5p, hsa-miR-187-5p, hsa-miR-3184-5p, hsa-miR-204-3p, hsa-miR-5572, hsa-miR-6729-5p, hsa-miR-615-5p, hsa-miR-6749-5p, hsa-miR-6515-3p, hsa-miR-3937, hsa-miR-6840-3p, hsa-miR-6893-5p, hsa-miR-4728-5p, hsa-miR-6717-5p, hsa-miR-7113-3p, hsa-miR-4665-5p, hsa-miR-642b-3p, hsa-miR-7109-5p, hsa-miR-6842-5p, hsa-miR-4442, hsa-miR-4433-3p, hsa-miR-4707-5p, hsa-miR-6126, represented by Array Numbers 1 to 194 and 606 to 614hsa-miR-4449, hsa-miR-4706, hsa-miR-1913, hsa-miR-602, hsa-miR-939-5p, hsa-miR-4695-5p, hsa-miR-711, hsa-miR-6816-5p, hsa-miR-4632-5p, hsa-miR-6721-5p, hsa-miR-7847-3p, hsa-miR-6132, hsa-miR-887-3p, hsa-miR-3679-3p, hsa-miR-6784-5p, hsa-miR-1249, hsa-miR-937-5p, hsa-miR-5195-3p, hsa-miR-6732-5p, hsa-miR-4417, hsa-miR-4281, hsa-miR-4734, hsa-miR-6766-3p, hsa-miR-663a, hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-1227-5p, hsa-miR-6845-5p, hsa-miR-6798-5p, hsa-miR-3620-5p, hsa-miR-1915-5p, hsa-miR-4294, hsa-miR-642a-3p, hsa-miR-371a-5p, hsa-miR-940, hsa-miR-4450, hsa-miR-4723-5p, hsa-miR-1469, hsa-miR-6861-5p, hsa-miR-7975, hsa-miR-6879-5p, hsa-miR-6802-5p, hsa-miR-1268b, hsa-miR-663b, hsa-miR-125a-3p, hsa-miR-2861, hsa-miR-6088, hsa-miR-4758-5p, hsa-miR-296-3p, hsa-miR-6738-5p, hsa-miR-671-5p, hsa-miR-4454, hsa-miR-4516, hsa-miR-7845-5p, hsa-miR-4741, hsa-miR-92b-5p, hsa-miR-6795-5p, hsa-miR-6805-3p, hsa-miR-4725-3p, hsa-miR-6782-5p, hsa-miR-4688, hsa-miR-6850-5p, hsa-miR-6777-5p, hsa-miR-6785-5p, hsa-miR-7106-5p, hsa-miR-3663-3p, hsa-miR-6131hsa-miR-1915-3p, hsa-miR-4532, hsa-miR-6820-5p, hsa-miR-4689, hsa-miR-4638-5p, hsa-miR-3656, hsa-miR-3621, hsa-miR-6769b-5p, hsa-miR-149-3p, hsa-miR-23b-3p, hsa-miR-3135b, hsa-miR-6848-5p, hsa-miR-6769a-5p, hsa-miR-4327, hsa-miR-6765-3p, hsa-miR-6716-5p, hsa-miR-6877-5p, hsa-miR-6727-5p, hsa-miR-4534, hsa-miR-614, hsa-miR-1202, hsa-miR-575, hsa-miR-6870-5p, hsa-miR-6722-3p, hsa-miR-7977, hsa-miR-4649-5p, hsa-miR-4675, hsa-miR-6075, hsa-miR-6779-5p, hsa-miR-4271, hsa-miR-3196, hsa-miR-6803-5p, hsa-miR-6789-5p, hsa-miR-4648, hsa-miR-4508, hsa-miR-4749-5p, hsa-miR-4505, hsa-miR-5698, hsa-miR-1199-5p, hsa-miR-4763-3p, hsa-miR-1231, hsa-miR-1233-5p, hsa-miR-150-3p, hsa-miR-1225-3p, hsa-miR-92a-2-5p, hsa-miR-423-5p, hsa-miR-1268a, hsa-miR-128-2-5p, hsa-miR-24-3p, hsa-miR-4697-5p, hsa-miR-3197, hsa-miR-675-5p, hsa-miR-4486, hsa-miR-7107-5p, hsa-miR-23a-3p, hsa-miR-4667-5p, hsa-miR-451a, hsa-miR-3940-5p, hsa-miR-8059, hsa-miR-6813-5p, hsa-miR-4492, hsa-miR-4476, hsa-miR-6090, hsa-miR-6836-3p, hsa-miR-3195, hsa-miR-718, hsa-miR-3178, hsa-miR-638, hsa-miR-4497hsa-miR-6085, hsa-miR-6752-5p, and hsa-miR-135a-3p are known, and their acquisition methods are also known as described above. Therefore, by cloning this gene, polynucleotides can be prepared as nucleic acid probes or primers that can be used in the present invention.

[0503] Such nucleic acid probes or primers can be chemically synthesized using a DNA automatic synthesizer. Generally, the phosphoramidite method is used for this synthesis, and single-stranded DNA up to about 100 bases can be automatically synthesized by this method. DNA automatic synthesizers are commercially available from, for example, Polygen, ABI, Applied BioSystems, etc.

[0504] Alternatively, the polynucleotides of the present invention can also be prepared by the cDNA cloning method. For cDNA cloning technology, for example, microRNA Cloning Kit Wako can be used.

[0505] Here, the sequences of the nucleic acid probes and primers for detecting polynucleotides consisting of the base sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 do not exist in vivo as miRNAs or their precursors. For example, the base sequences represented by SEQ ID NO: 11 and SEQ ID NO: 78 are generated from the precursor represented by SEQ ID NO: 205, but this precursor has a hairpin-like structure as shown in FIG. 1, and the base sequences represented by SEQ ID NO: 11 and SEQ ID NO: 78 have mismatched sequences with each other. Similarly, a completely complementary base sequence to the base sequence represented by SEQ ID NO: 11 or SEQ ID NO: 78 is not naturally generated in vivo. Therefore, the nucleic acid probes and primers for detecting the base sequences represented by any of SEQ ID NOs: 1 to 194 and 606 to 614 will have artificial base sequences that do not exist in vivo.

[0506] 3. Kit or device for detecting colorectal cancer The present invention also provides a kit or device for detecting colorectal cancer, which contains one or more polynucleotides (which may include variants, fragments, or derivatives, and may hereinafter be referred to as polynucleotides for detection) that can be used as nucleic acid probes or primers in the present invention for measuring a target nucleic acid that is a colorectal cancer marker.

[0507] The target nucleic acid that is a colorectal cancer marker in the present invention is preferably selected from the following Group 1: miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-204-3p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-3937, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p, miR-1227-5pmiR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085, miR-6752-5p and miR-135a-3p.,

[0508] Additional target nucleic acids that may optionally be used for measurement are selected from the following Group 2: miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, and miR-24-3p.

[0509] Additional target nucleic acids that may further optionally be used for measurement are selected from the following Group 3: miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, and miR-6090.

[0510] The kit or device of the present invention contains a nucleic acid that can specifically bind to the target nucleic acid that is the above-mentioned colorectal cancer marker, preferably a nucleic acid probe or primer described in the above item 2, specifically one or more polynucleotides selected from the polynucleotides described in the above item 2 or variants thereof, etc.

[0511] Specifically, the kit or device of the present invention can contain at least one or more of a polynucleotide represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a polynucleotide having a base sequence in which u is t in the said base sequence, a polynucleotide containing (or consisting of) its complementary sequence, a polynucleotide that hybridizes with those polynucleotides under stringent conditions, or a variant or fragment containing 15 or more consecutive bases of those polynucleotide sequences.

[0512] The kit or device of the present invention may further include one or more polynucleotides comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 172 to 180, or a nucleotide sequence in which u is t in the nucleotide sequence, a polynucleotide comprising (or consisting of) its complementary sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant or fragment comprising 15 or more consecutive bases of these polynucleotide sequences.

[0513] The kit or device of the present invention may further include one or more polynucleotides comprising (or consisting of) a nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, a polynucleotide comprising (or consisting of) its complementary sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant or fragment comprising 15 or more consecutive bases of these polynucleotide sequences.

[0514] The fragment that can be included in the kit or device of the present invention is, for example, one or more, preferably two or more polynucleotides selected from the group consisting of the following (1) to (3). (1) A polynucleotide comprising 15 or more consecutive bases in a nucleotide sequence in which u is t in the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or in its complementary sequence. (2) A polynucleotide comprising 15 or more consecutive bases in a nucleotide sequence in which u is t in the nucleotide sequence represented by any of SEQ ID NOs: 172 to 180, or in its complementary sequence. (3) A polynucleotide comprising 15 or more consecutive bases in a nucleotide sequence in which u is t in the nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or in its complementary sequence.

[0515] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of its complementary sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.

[0516] Also, in a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of its complementary sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.

[0517] Also, in a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 181 to 194, or a base sequence in which u is t in the base sequence, a polynucleotide consisting of its complementary sequence, a polynucleotide that hybridizes with these polynucleotides under stringent conditions, or a variant containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases thereof.

[0518] In a preferred embodiment, the fragment can be a polynucleotide containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.

[0519] In the present invention, the size of the fragment of the polynucleotide is, in the base sequence of each polynucleotide, for example, the number of bases in the range from 15 consecutive bases to less than the total number of bases in the sequence, from 17 consecutive bases to less than the total number of bases in the sequence, from 19 consecutive bases to less than the total number of bases in the sequence, and the like.

[0520] As the combination of the above polynucleotides constituting the kit or device of the present invention, specifically, the above polynucleotides consisting of the base sequences represented by the SEQ ID Nos. shown in Table 1 (SEQ ID Nos. 1 to 194 and 606 to 614 corresponding to the miRNA markers in the table) can be combined in 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more numbers, but these are merely examples, and all other various possible combinations shall be included in the present invention.

[0521] For example, as the above combination constituting the kit or device for discriminating colorectal cancer from a healthy body in the present invention, it is desirable to combine 2 or more of the above polynucleotides consisting of the base sequences represented by the SEQ ID Nos. shown in Table 1, and usually a combination of 2 can obtain sufficient performance.

[0522] Specifically, as a combination of 2 polynucleotides consisting of a base sequence or its complementary sequence for discriminating colorectal cancer from a healthy body, among the combinations of 2 polynucleotides consisting of the base sequences represented by SEQ ID Nos. 1 to 194 and 606 to 614, a combination containing at least 1 or more polynucleotides consisting of the base sequence represented by SEQ ID Nos. 1 to 171 newly found is preferable. More specifically, among the combinations of polynucleotides consisting of the base sequences represented by SEQ ID Nos. 1 to 194 and 606 to 614, a combination containing at least 1 polynucleotide consisting of the base sequence represented by SEQ ID Nos. 5, 15, 24, 32, 38, 45, 55, 64, 96, 97, 162 is more preferable.

[0523] In addition, as a combination of polynucleotides with cancer type specificity that can distinguish colorectal cancer not only from healthy subjects but also from other cancers, for example, at least one polynucleotide selected from the group consisting of the polynucleotides of SEQ ID NO: 5, 13, 15, 24, 32, 38, 41, 45, 55, 57, 64, 72, 75, 77, 96, 97, 115, 162, 163, 173, 189, 606, 607, 608, 609, 610, 611, 612, 613, and 614 (hereinafter, this group will be referred to as "cancer type specific polynucleotide group 1") and a plurality of combinations with polynucleotides of other SEQ ID NOs are preferred.

[0524] Furthermore, as a combination of polynucleotides with cancer type specificity that can distinguish colorectal cancer not only from healthy subjects but also from other cancers, a combination of a plurality of polynucleotides selected from cancer type specific polynucleotide group 1 is more preferred.

[0525] Furthermore, as a combination of polynucleotides with cancer type specificity that can distinguish colorectal cancer not only from healthy subjects but also from other cancers, among the combinations of a plurality of polynucleotides selected from cancer type specific polynucleotide group 1, a combination containing at least one polynucleotide selected from the group consisting of the polynucleotides of SEQ ID NO: 5, 45, 57, 96, and 606 included in cancer type specific polynucleotide group 1 (hereinafter, this group will be referred to as "cancer type specific polynucleotide group 2") is more preferred.

[0526] The number of combinations of the above-mentioned polynucleotides with cancer type specificity can be a combination of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more, but more preferably a combination of 6 or more, and usually a combination of 5 or 6 can obtain sufficient performance.

[0527] The following are non-limiting examples of combinations of a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO:5 or its complementary sequence and 4 or 5 polynucleotides selected from the cancer species-specific polynucleotide group 1, represented by the SEQ ID NO: of the nucleotide sequence represented by the SEQ ID NO: or its complementary sequence.

[0528] (1) Combination of SEQ ID NO:5, 45, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3195) (2) Combination of SEQ ID NO:5, 45, 96, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-3195) (3) Combination of SEQ ID NO:5, 45, 57, 97, 115, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-642a-3p, hsa-miR-671-5p, hsa-miR-3195) (4) Combination of SEQ ID NO:5, 45, 57, 97, 162, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-642a-3p, hsa-miR-3196, hsa-miR-3195) (5) Combination of SEQ ID NO:5, 45, 57, 162, 607, 613 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3196, hsa-miR-3195, hsa-miR-6752-5p) (6) Combination of SEQ ID NO:5, 45, 57, 97, 607, 612 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-642a-3p, hsa-miR-3195, hsa-miR-6085) (7) Combinations of SEQ ID NO: 5, 13, 45, 57, 606, 607 (markers: hsa-miR-3131, hsa-miR-6746-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-6836-3p, hsa-miR-3195) (8) Combinations of SEQ ID NO: 5, 45, 96, 189, 606, 608 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p, hsa-miR-718) (9) Combinations of SEQ ID NO: 5, 45, 57, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p) (10) Combinations of SEQ ID NO: 5, 24, 45, 57, 96, 608 (markers: hsa-miR-3131, hsa-miR-6826-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-718) (11) Combinations of SEQ ID NO: 5, 45, 57, 162, 607, 610 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3196, hsa-miR-3195, hsa-miR-638) (12) Combinations of SEQ ID NO: 5, 45, 57, 189, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3940-5p, hsa-miR-6836-3p, hsa-miR-3195)

[0529] Furthermore, non-limiting examples include combinations of a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 45 or its complementary sequence and four or five polynucleotides selected from the group of cancer species-specific polynucleotides, which are represented by the sequence numbers of the nucleotide sequences consisting of the nucleotide sequences represented by the sequence numbers or their complementary sequences.

[0530] (1) Combinations of SEQ ID NO: 5, 45, 96, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-3195) (2) Combinations of SEQ ID NO: 5, 45, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3195) (3) Combinations of SEQ ID NO: 5, 45, 57, 75, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-6836-3p, hsa-miR-3195) (4) Combinations of SEQ ID NO: 5, 45, 57, 77, 607, 613 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-887-3p, hsa-miR-3195, hsa-miR-6752-5p) (5) Combinations of SEQ ID NO: 5, 45, 57, 97, 606, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-642a-3p, hsa-miR-6836-3p, hsa-miR-3195) (6) Combinations of SEQ ID NO: 5, 45, 57, 75, 77, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-887-3p, hsa-miR-3195) (7) Combinations of SEQ ID NO: 5, 32, 45, 57, 96, 606 (markers: hsa-miR-3131, hsa-miR-8069, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-6836-3p) (8) The combination of SEQ ID NO: 5, 24, 45, 57, 96, 606 (markers: hsa-miR-3131, hsa-miR-6826-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-6836-3p) (9) The combination of SEQ ID NO: 5, 45, 57, 96, 162, 606 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-3196, hsa-miR-6836-3p) (10) The combination of SEQ ID NO: 5, 15, 45, 75, 96, 606 (markers: hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-204-3p, hsa-miR-7847-3p, hsa-miR-4294, hsa-miR-6836-3p) (11) The combination of SEQ ID NO: 5, 32, 45, 57, 162, 607 (markers: hsa-miR-3131, hsa-miR-8069, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3196, hsa-miR-3195) (12) The combination of SEQ ID NO: 38, 45, 96, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497)

[0531] Furthermore, non-limitingly, an example is given of a combination of a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 57 or its complementary sequence and a polynucleotide consisting of the nucleotide sequence represented by the SEQ ID NO: of 4 or 5 polynucleotides selected from the group of cancer type-specific polynucleotides 1 or its complementary sequence.

[0532] (1) Combinations of SEQ ID NO: 24, 41, 57, 45, 96 (markers: hsa-miR-6826-5p, hsa-miR-4419b, hsa-miR-4665-5p, hsa-miR-204-3p, hsa-miR-4294) (2) Combinations of SEQ ID NO: 5, 45, 57, 607, 612 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-3195, hsa-miR-6085) (3) Combinations of SEQ ID NO: 5, 45, 57, 606, 607, 608 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-6836-3p, hsa-miR-3195, hsa-miR-718) (4) Combinations of SEQ ID NO: 5, 13, 45, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-6746-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3195) (5) Combinations of SEQ ID NO: 5, 45, 57, 64, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-6126, hsa-miR-7847-3p, hsa-miR-3195) (6) Combinations of SEQ ID NO: 5, 45, 55, 57, 607, 613 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-6717-5p, hsa-miR-4665-5p, hsa-miR-3195, hsa-miR-6752-5p) (7) Combinations of SEQ ID NO: 5, 45, 55, 57, 75, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-6717-5p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3195) (8) A combination of SEQ ID NO: 5, 38, 45, 57, 96, 607 (markers: hsa-miR-3131, hsa-miR-6724-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-3195) (9) A combination of SEQ ID NO: 5, 45, 57, 75, 162, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3196, hsa-miR-3195) (10) A combination of SEQ ID NO: 5, 45, 57, 75, 162, 609 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-3196, hsa-miR-3178) (11) A combination of SEQ ID NO: 5, 45, 57, 64, 96, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-6126, hsa-miR-4294, hsa-miR-3195) (12) A combination of SEQ ID NO: 57, 64, 96, 606, 608, 611 (markers: hsa-miR-4665-5p, hsa-miR-6126, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497)

[0533] Furthermore, non-limitingly, an example is given of a combination of a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 96 or its complementary sequence and four or five polynucleotides selected from the group of cancer species-specific polynucleotides 1, which are represented by the nucleotide sequences represented by SEQ ID NOs.

[0534] (1) A combination of SEQ ID NO: 38, 96, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497) (2) Combinations of SEQ ID NO: 5, 45, 57, 96, 607 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-3195) (3) Combinations of SEQ ID NO: 38, 72, 96, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-6816-5p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497) (4) Combinations of SEQ ID NO: 32, 38, 96, 606, 608, 611 (markers: hsa-miR-8069, hsa-miR-6724-5p, hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497) (5) Combinations of SEQ ID NO: 38, 96, 163, 606, 608, 611 (markers: hsa-miR-6724-5p, hsa-miR-4294, hsa-miR-6803-5p, hsa-miR-6836-3p, hsa-miR-718, hsa-miR-4497) (6) Combinations of SEQ ID NO: 64, 72, 96, 162, 609, 611 (markers: hsa-miR-6126, hsa-miR-6816-5p, hsa-miR-4294, hsa-miR-3196, hsa-miR-3178, hsa-miR-4497) (7) Combinations of SEQ ID NO: 38, 64, 96, 163, 606, 608 (markers: hsa-miR-6724-5p, hsa-miR-6126, hsa-miR-4294, hsa-miR-6803-5p, hsa-miR-6836-3p, hsa-miR-718) (8) Combinations of SEQ ID NO: 5, 45, 57, 75, 96, 606 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-7847-3p, hsa-miR-4294, hsa-miR-6836-3p) (9) Combinations of SEQ ID NO: 5, 15, 45, 57, 96, 606 (markers: hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-6836-3p) (10) Combinations of SEQ ID NO: 5, 41, 45, 57, 96, 606 (markers: hsa-miR-3131, hsa-miR-4419b, hsa-miR-204-3p, hsa-miR-4665-5p, hsa-miR-4294, hsa-miR-6836-3p) (11) Combinations of SEQ ID NO: 5, 41, 45, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-4419b, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p) (12) Combinations of SEQ ID NO: 5, 45, 75, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-7847-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p)

[0535] Furthermore, non-limitingly, an example is given of a combination of a polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 606 or its complementary sequence and a polynucleotide consisting of the nucleotide sequence represented by the SEQ ID NO: of three polynucleotides selected from the group of cancer species-specific polynucleotides 1 or its complementary sequence.

[0536] (1) Combinations of SEQ ID NO: 5, 24, 45, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-6826-5p, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p) (2) Combinations of SEQ ID NO: 5, 15, 45, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p) (3) Combinations of SEQ ID NO: 5, 45, 96, 189, 606, 613 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p, hsa-miR-6752-5p) (4) Combinations of SEQ ID NO: 5, 45, 72, 96, 189, 606 (markers: hsa-miR-3131, hsa-miR-204-3p, hsa-miR-6816-5p, hsa-miR-4294, hsa-miR-3940-5p, hsa-miR-6836-3p) (5) Combinations of SEQ ID NO: 5, 15, 32, 45, 96, 606 (markers: hsa-miR-3131, hsa-miR-6741-5p, hsa-miR-8069, hsa-miR-204-3p, hsa-miR-4294, hsa-miR-6836-3p)

[0537] In addition to the polynucleotides of the present invention described above (which may include variants, fragments or derivatives), the kits or devices of the present invention can also include known polynucleotides that enable the detection of colorectal cancer or polynucleotides that will be discovered in the future.

[0538] The kits of the present invention can also include antibodies for measuring known colorectal cancer markers such as CEA and CA19-9 in addition to the polynucleotides of the present invention described above.

[0539] The above polynucleotides included in the kits of the present invention can be individually or arbitrarily combined and packaged in different containers.

[0540] The kit of the present invention can include a kit for extracting nucleic acids (e.g., total RNA) from body fluids, cells, or tissues, a fluorescent substance for labeling, an enzyme for nucleic acid amplification, a medium, an instruction manual, and the like.

[0541] The device of the present invention is a device for measuring cancer markers in which nucleic acids such as the polynucleotides in the present invention described above are bound or attached to a solid phase, for example. Examples of the material of the solid phase are plastic, paper, glass, silicon, etc. From the ease of processing, the preferred material of the solid phase is plastic. The shape of the solid phase is arbitrary, for example, square, round, strip-shaped, film-shaped, etc. The device of the present invention includes, for example, a device for measurement by hybridization technology, and specifically, a blotting device, a nucleic acid array (e.g., a microarray, a DNA chip, an RNA chip, etc.) and the like are exemplified.

[0542] Nucleic acid array technology is a method of spotting nucleic acids on the surface of a solid phase that has been surface-treated, such as coating with L-lysine or introducing functional groups such as amino groups and carboxyl groups as needed, using a high-density dispenser called a spotter or an arrayer, a method of spraying nucleic acids onto a solid phase using an inkjet that injects minute droplets from a nozzle by a piezoelectric element or the like, a method of sequentially performing nucleotide synthesis on a solid phase, etc., to bind or attach the above nucleic acids one by one to produce an array such as a chip, and measuring a target nucleic acid using hybridization with this array.

[0543] The kit or device of the present invention contains nucleic acids that can specifically bind to each of all polynucleotides from at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more of the miRNAs that are colorectal cancer markers of the above-mentioned Group 1. The kit or device of the present invention can further optionally contain nucleic acids that can specifically bind to each of all polynucleotides from at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more of the miRNAs that are colorectal cancer markers of the above-mentioned Group 2. The kit or device of the present invention can further optionally contain nucleic acids that can specifically bind to each of all polynucleotides from at least one or more, preferably at least two or more, more preferably at least three or more, and most preferably at least five or more of the miRNAs that are colorectal cancer markers of the above-mentioned Group 3.

[0544] The kit or device of the present invention can be used for the detection of the following colorectal cancer.

[0545] 4. Method for Detecting Colorectal Cancer The present invention further uses the kit or device of the present invention described in 3 above (including the above nucleic acids that can be used in the present invention) to detect, in a sample, the following group: miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-204-3p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-3937, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281,miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p, miR-1227-5p, miR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085The expression level of a gene derived from colorectal cancer selected from miR-6752-5p and miR-135a-3p, and optionally, the expression level of a gene derived from colorectal cancer selected from the following group: miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, and miR-24-3p, and optionally, the expression level of a gene derived from colorectal cancer selected from the following group: miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, and miR-6090, is measured in vitro. Further, for specimens such as blood, serum, and plasma collected from a subject suspected of having colorectal cancer and a healthy subject (including non-colorectal cancer patients), using the expression level of the above gene in the specimen and the control expression level of the healthy subject, for example, by comparing both expression levels, when there is a statistically significant difference in the expression level of the target nucleic acid in the specimen, it includes evaluating that the subject has colorectal cancer. A method for detecting colorectal cancer is provided.

[0546] The above method of the present invention enables minimally invasive, highly sensitive, and highly specific early diagnosis of cancer, thereby leading to early treatment and improved prognosis. Furthermore, it enables monitoring of disease aversion and monitoring the effectiveness of surgical, radiotherapy, and chemotherapy treatments.

[0547] In the method for extracting a gene derived from colorectal cancer from a specimen such as blood, serum, or plasma of the present invention, it is particularly preferable to prepare by adding an RNA extraction reagent in 3D-Gene (registered trademark) RNA extraction reagent from liquid sample kit (Toray Industries, Inc.). However, a general acid phenol method (Acid Guanidinium-Phenol-Chloroform (AGPC) method) may be used, or Trizol (registered trademark) (Life Technologies) may be used, or an RNA extraction reagent containing acid phenol such as Trizol (Life Technologies) or Isogen (Nippon Gene) may be added for preparation. Furthermore, kits such as miRNeasy (registered trademark) Mini Kit (Qiagen) can be used, but the method is not limited to these.

[0548] The present invention also provides the use of the kit or device of the present invention for the in vitro detection of the expression product of a miRNA gene derived from colorectal cancer in a specimen from a subject.

[0549] In the above method of the present invention, as the kit or device, those containing the polynucleotide that can be used in the present invention as described above, either singly or in any possible combination, are used.

[0550] In the detection or (gene) diagnosis of colorectal cancer of the present invention, the polynucleotide contained in the kit or device of the present invention can be used as a probe or a primer. When used as a primer, TaqMan (registered trademark) MicroRNA Assays of Life Technologies, miScript PCR System of Qiagen, etc. can be used, but the method is not limited to these.

[0551] The polynucleotides included in the kit or device of the present invention can be used as primers or probes according to established methods in known methods for specifically detecting a specific gene, such as hybridization techniques including Northern blotting, Southern blotting, in situ hybridization, Northern hybridization, Southern hybridization, etc., and quantitative amplification techniques such as quantitative RT-PCR. As the specimen to be measured, depending on the type of detection method used, body fluids such as the blood, serum, plasma, urine, etc. of the subject are collected. Alternatively, total RNA prepared by the above method on such body fluids may be used, or various polynucleotides including cDNA prepared based on the RNA may also be used.

[0552] The kit or device of the present invention is useful for the diagnosis of colorectal cancer or the detection of the presence or absence of the disease. Specifically, the detection of colorectal cancer using the kit or device can be performed by detecting in vitro the expression level of a gene detected by a nucleic acid probe or primer included in the kit or device using specimens such as blood, serum, plasma, urine, etc. from a subject suspected of having colorectal cancer. When the expression level of the target miRNA marker measured by a polynucleotide (including its variants, fragments or derivatives) consisting of at least one or more of the base sequences represented by SEQ ID NOs: 1 to 171 and 606 to 614, and optionally one or more of the base sequences represented by SEQ ID NOs: 172 to 180 or their complementary sequences, and optionally one or more of the base sequences represented by SEQ ID NOs: 181 to 194 or their complementary sequences, in specimens such as the blood, serum, plasma, urine, etc. of a subject suspected of having colorectal cancer is statistically significantly different from their expression levels in specimens such as the blood, serum, or plasma, urine, etc. of a healthy subject, the subject can be evaluated as having colorectal cancer.

[0553] The method of the present invention can be combined with imaging diagnostic methods such as enema imaging, CT examination, MRI examination, bone scintigraphy examination, etc. in addition to fecal occult blood test, digital rectal examination, and colonoscopy. The method of the present invention can specifically detect colorectal cancer and can be substantially distinguished from cancers other than colorectal cancer.

[0554] The detection method for the absence or presence of the expression product of a gene derived from colorectal cancer in a specimen using the kit or device of the present invention includes collecting body fluids such as the blood, serum, plasma, urine, etc. of a subject and measuring the expression level of the target gene contained therein using one or more polynucleotides selected from the polynucleotide group of the present invention (including variants, fragments or derivatives), so as to evaluate the presence or absence of colorectal cancer or detect colorectal cancer. Also, using the detection method for colorectal cancer of the present invention, for example, in a colorectal cancer patient, it is also possible to evaluate or diagnose the presence or absence or degree of improvement of the disease when a therapeutic agent is administered for the improvement of the disease.

[0555] The method of the present invention can include, for example, the following steps (a), (b) and (c): (a) A step of contacting a specimen derived from a subject with the polynucleotide in the kit or device of the present invention in vitro; (b) A step of measuring the expression level of the target nucleic acid in the specimen using the polynucleotide as a nucleic acid probe or primer; (c) A step of evaluating the presence or absence of colorectal cancer (cells) in the subject based on the result of (b). can be included.

[0556] Specifically, the present invention relates to miR-6726-5p, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-204-3p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-3937, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p,At least one selected from the group consisting of miR-1227-5p, miR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085, miR-6752-5p, and miR-135a-3p,Preferably, a nucleic acid capable of specifically binding to at least two or more polynucleotides is used to measure the expression level of a target nucleic acid in a specimen of a subject, and the measured expression level and a control expression level of a healthy subject measured in the same manner are used to evaluate in vitro whether the subject has colorectal cancer or does not have colorectal cancer. Provided is a method for detecting colorectal cancer, including

[0557] As used herein, "evaluate" refers to evaluation support based on the results of in vitro tests, rather than a determination by a physician.

[0558] As described above, in the method of a preferred embodiment of the present invention, the target nucleic acid is specifically miR-6726-5p is hsa-miR-6726-5p, miR-4257 is hsa-miR-4257, and miR-6787-5p is hsa-miR-6787 -5p, miR-6780b-5p is hsa-miR-6780b-5p, miR-3131 is hsa-miR-3131, miR-7108-5p is hsa-miR-7108-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1247-3p is hsa-miR-1247-3p, miR-4651 is hsa-miR-4651, miR-6757-5p is hsa-miR-6757-5p, miR-3679-5p is hsa-miR-3679-5p, miR-7641 is hsa-miR-7641, miR-6746-5p is hsa-miR-6746-5p, miR-8072 is hsa-miR-8072, miR-6741-5p is hsa-miR-6741-5p, miR-1908-5p is hsa-miR-1908-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4746-3p is hsa-miR-4746-3p, miR-744-5p is hsa-miR-744-5p, miR-4792 is hsa-miR-4792, miR-564 is hsa-miR-564, miR-6791-5p is hsa-miR-6791-5p, miR-6825-5p is hsa-miR-6825-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4665-3p is hsa-miR-4665-3p, miR-4467 is hsa-miR-4467, miR-3188 is hsa-miR-3188, miR-6125 is hsa-miR-6125, miR-6756-5p is hsa-miR-6756-5p, miR-1228-3p is hsa-miR-1228-3p, miR-8063 is hsa-miR-8063, miR-8069 is hsa-miR-8069, miR-6875-5p is hsa-miR-6875-5p, miR-3185 is hsa-miR-3185, miR-4433b-3p is hsa-miR-4433b-3p, miR-6887-5p is hsa-miR-6887-5p, miR-128-1-5p is hsa-miR-128-1-5p,miR-6724-5p is hsa-miR-6724-5p, miR-1914-3p is hsa-miR-1914-3p, miR-1225-5p is hsa-miR-1225-5p, miR-4419b is hsa-miR-4419b, miR-7110-5p is hsa-miR-7110-5p, miR-187-5p is hsa-miR-187-5p, miR-3184-5p is hsa-miR-3184-5p, miR-204-3p is hsa-miR-204-3p, miR-5572 is hsa-miR-5572, miR-6729-5p is hsa-miR-6729-5p, miR-615-5p is hsa-miR-615-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6515-3p is hsa-miR-6515-3p, miR-3937 is hsa-miR-3937, miR-6840-3p is hsa-miR-6840-3p, miR-6893-5p is hsa-miR-6893-5p, miR-4728-5p is hsa-miR-4728-5p, miR-6717-5p is hsa-miR-6717-5p, miR-7113-3p is hsa-miR-7113-3p, miR-4665-5p is hsa-miR-4665-5p, miR-642b-3p is hsa-miR-642b-3p, miR-7109-5p is hsa-miR-7109-5p, miR-6842-5p is hsa-miR-6842-5p, miR-4442 is hsa-miR-4442, miR-4433-3p is hsa-miR-4433-3p, miR-4707-5p is hsa-miR-4707-5p, miR-6126 is hsa-miR-6126, miR-4449 is hsa-miR-4449, miR-4706 is hsa-miR-4706, miR-1913 is hsa-miR-1913, miR-602 is hsa-miR-602, miR-939-5p is hsa-miR-939-5p, miR-4695-5p is hsa-miR-4695-5p, miR-711 is hsa-miR-711,miR-6816-5p is hsa-miR-6816-5p, miR-4632-5p is hsa-miR-4632-5p, miR-6721-5p is hsa-miR-6721-5p, miR-7847-3p is hsa-miR-7847-3p, miR-6132 is hsa-miR-6132, miR-887-3p is hsa-miR-887-3p, miR-3679-3p is hsa-miR-3679-3p, miR-6784-5p is hsa-miR-6784-5p, miR-1249 is hsa-miR-1249, miR-937-5p is hsa-miR-937-5p, miR-5195-3p is hsa-miR-5195-3p, miR-6732-5p is hsa-miR-6732-5p, miR-4417 is hsa-miR-4417, miR-4281 is hsa-miR-4281, miR-4734 is hsa-miR-4734, miR-6766-3p is hsa-miR-6766-3p, miR-663a is hsa-miR-663a, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p, miR-1227-5p is hsa-miR-1227-5p, miR-6845-5p is hsa-miR-6845-5p, miR-6798-5p is hsa-miR-6798-5p, miR-3620-5p is hsa-miR-3620-5p, miR-1915-5p is hsa-miR-1915-5p, miR-4294 is hsa-miR-4294, miR-642a-3p is hsa-miR-642a-3p, miR-371a-5p is hsa-miR-371a-5p, miR-940 is hsa-miR-940, miR-4450 is hsa-miR-4450, miR-4723-5p is hsa-miR-4723-5p, miR-1469 is hsa-miR-1469, miR-6861-5p is hsa-miR-6861-5p, miR-7975 is hsa-miR-7975, miR-6879-5p is hsa-miR-6879-5p,miR-6802-5p is hsa-miR-6802-5p, miR-1268b is hsa-miR-1268b, miR-663b is hsa-miR-663b, miR-125a-3p is hsa-miR-125a-3p, miR-2861 is hsa-miR-2861, miR-6088 is hsa-miR-6088, miR-4758-5p is hsa-miR-4758-5p, miR-296-3p is hsa-miR-296-3p, miR-6738-5p is hsa-miR-6738-5p, miR-671-5p is hsa-miR-671-5p, miR-4454 is hsa-miR-4454, miR-4516 is hsa-miR-4516, miR-7845-5p is hsa-miR-7845-5p, miR-4741 is hsa-miR-4741, miR-92b-5p is hsa-miR-92b-5p, miR-6795-5p is hsa-miR-6795-5p, miR-6805-3p is hsa-miR-6805-3p, miR-4725-3p is hsa-miR-4725-3p, miR-6782-5p is hsa-miR-6782-5p, miR-4688 is hsa-miR-4688, miR-6850-5p is hsa-miR-6850-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6785-5p is hsa-miR-6785-5p, miR-7106-5p is hsa-miR-7106-5p, miR-3663-3p is hsa-miR-3663-3p, miR-6131 is hsa-miR-6131, miR-1915-3p is hsa-miR-1915-3p, miR-4532 is hsa-miR-4532, miR-6820-5p is hsa-miR-6820-5p, miR-4689 is hsa-miR-4689, miR-4638-5p is hsa-miR-4638-5p, miR-3656 is hsa-miR-3656, miR-3621 is hsa-miR-3621, miR-6769b-5p is hsa-miR-6769b-5p,miR-149-3p is hsa-miR-149-3p, miR-23b-3p is hsa-miR-23b-3p, miR-3135b is hsa-miR-3135b, miR-6848-5p is hsa-miR-6848-5p, miR-6769a-5p is hsa-miR-6769a-5p, miR-4327 is hsa-miR-4327, miR-6765-3p is hsa-miR-6765-3p, miR-6716-5p is hsa-miR-6716-5p, miR-6877-5p is hsa-miR-6877-5p, miR-6727-5p is hsa-miR-6727-5p, miR-4534 is hsa-miR-4534, miR-614 is hsa-miR-614, miR-1202 is hsa-miR-1202, miR-575 is hsa-miR-575, miR-6870-5p is hsa-miR-6870-5p, miR-6722-3p is hsa-miR-6722-3p, miR-7977 is hsa-miR-7977, miR-4649-5p is hsa-miR-4649-5p, miR-4675 is hsa-miR-4675, miR-6075 is hsa-miR-6075, miR-6779-5p is hsa-miR-6779-5p, miR-4271 is hsa-miR-4271, miR-3196 is hsa-miR-3196, miR-6803-5p is hsa-miR-6803-5p, miR-6789-5p is hsa-miR-6789-5p, miR-4648 is hsa-miR-4648, miR-4508 is hsa-miR-4508, miR-4749-5p is hsa-miR-4749-5p, miR-4505 is hsa-miR-4505, miR-5698 is hsa-miR-5698, miR-1199-5p is hsa-miR-1199-5p, miR-4763-3p is hsa-miR-4763-3p, miR-6836-3p is hsa-miR-6836-3p, miR-3195 is hsa-miR-3195, miR-718 is hsa-miR-718, miR-3178 is hsa-miR-3178,miR-638 is hsa-miR-638, miR-4497 is hsa-miR-4497, miR-6085 is hsa-miR-6085, miR-6752-5p is hsa-miR-6752-5p, and miR-135a-3p is hsa-miR-135a-3p.,

[0559] Also, in a preferred embodiment of the method of the present invention, specifically, the nucleic acid (specifically, a probe or primer) is a polynucleotide represented by any of the following (a) to (e): (a) A polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (b) A polynucleotide containing a nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, (c) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases, (d) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 171 and 606 to 614, or a nucleotide sequence in which u is t in the nucleotide sequence, and (e) A polynucleotide that hybridizes with any of the polynucleotides of (a) to (d) under stringent conditions, is selected from the group consisting of.

[0560] In the method of the present invention, furthermore, a nucleic acid that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, and miR-24-3p can be used.

[0561] Such nucleic acids are specifically miR-1231 being hsa-miR-1231, miR-1233-5p being hsa-miR-1233-5p, miR-150-3p being hsa-miR-150-3p, miR-1225-3p being hsa-miR-1225-3p, miR-92a-2-5p being hsa-miR-92a-2-5p, miR-423-5p being hsa-miR-423-5p, miR-1268a being hsa-miR-1268a, miR-128-2-5p being hsa-miR-128-2-5p, and miR-24-3p being hsa-miR-24-3p.

[0562] Furthermore, in a preferred embodiment, specifically, such nucleic acids are polynucleotides shown in the following (f) to (j): (f) A polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (g) A polynucleotide containing a base sequence represented by any of SEQ ID NOs: 172 to 180, (h) A polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (i) A polynucleotide containing a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 172 to 180, or a base sequence in which u is t in the base sequence, and (j) A polynucleotide that hybridizes with any of the polynucleotides of (f) to (i) under stringent conditions, selected from the group consisting of.

[0563] In the nucleic acid in the method of the present invention, nucleic acids that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, and miR-6090 can be used.

[0564] Specifically, such nucleic acids are such that miR-4697-5p is hsa-miR-4697-5p, miR-3197 is hsa-miR-3197, miR-675-5p is hsa-miR-675-5p, miR-4486 is hsa-miR-4486, miR-7107-5p is hsa-miR-7107-5p, miR-23a-3p is hsa-miR-23a-3p, miR-4667-5p is hsa-miR-4667-5p, miR-451a is hsa-miR-451a, miR-3940-5p is hsa-miR-3940-5p, miR-8059 is hsa-miR-8059, miR-6813-5p is hsa-miR-6813-5p, miR-4492 is hsa-miR-4492, miR-4476 is hsa-miR-4476, and miR-6090 is hsa-miR-6090.

[0565] Furthermore, in a preferred embodiment, specifically, such nucleic acids are the polynucleotides shown in the following (k) to (o): (k) A polynucleotide consisting of the nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the said nucleotide sequence, its variant, its derivative, or a fragment thereof containing 15 or more consecutive bases (l) A polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, (m) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases. (n) A polynucleotide containing a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 181 to 194, or a nucleotide sequence in which u is t in the nucleotide sequence, and (o) A polynucleotide that hybridizes under stringent conditions with any of the polynucleotides of (k) to (n) above. A polynucleotide selected from the group consisting of.

[0566] Examples of the sample used in the method of the present invention include samples prepared from a subject's biological tissue (preferably, colon tissue), body fluids such as blood, serum, plasma, urine, etc. Specifically, an RNA-containing sample prepared from the tissue, a sample containing a polynucleotide further prepared therefrom, body fluids such as blood, serum, plasma, urine, a part or all of the subject's biological tissue collected by biopsy or the like, or a biological tissue excised by surgery, etc., and a sample for measurement can be prepared from these.

[0567] As used herein, the subject refers to a mammal, such as, but not limited to, a human, a monkey, a mouse, a rat, etc., preferably a human.

[0568] The method of the present invention can change the steps according to the type of sample used as the measurement target.

[0569] When using RNA as the measurement target, the detection of colorectal cancer (cells) is, for example, the following steps (a), (b) and (c): (a) A step of binding RNA prepared from a subject's sample or a complementary polynucleotide (cDNA) transcribed therefrom to the polynucleotide in the kit or device of the present invention. (b) Measuring the RNA derived from the specimen bound to the polynucleotide or the cDNA synthesized from the RNA by hybridization using the polynucleotide as a nucleic acid probe, or by quantitative RT-PCR using the polynucleotide as a primer; (c) Evaluating the presence or absence of colorectal cancer (gene expression derived therefrom) based on the measurement result in (b); may be included.

[0570] For detecting, examining, evaluating or diagnosing colorectal cancer (gene expression derived therefrom) in vitro according to the present invention, for example, various hybridization methods can be used. Such hybridization methods include, for example, Northern blotting, Southern blotting, RT-PCR, DNA chip analysis, in situ hybridization, Northern hybridization, Southern hybridization, etc.

[0571] When using the Northern blotting method, the presence or absence and the expression level of each gene expression in RNA can be detected and measured by using the nucleic acid probe usable in the present invention. Specifically, a nucleic acid probe (complementary strand) is labeled with a radioisotope (such as 32P, 33P, 35S) or a fluorescent substance, and after hybridizing it with the RNA derived from the biological tissue of the subject transferred to a nylon membrane or the like according to a conventional method, the signal derived from the label (radioisotope or fluorescent substance) of the formed DNA / RNA double strand is detected and measured by a radiation detector (such as BAS-1800II (Fuji Photo Film Co., Ltd.)) or a fluorescence detector (such as STORM 865 (GE Healthcare)). A method for detection and measurement can be exemplified.

[0572] When using the quantitative RT-PCR method, the presence or absence and the expression level of a gene in RNA can be detected and measured by using the above primers that can be used in the present invention. Specifically, cDNA is prepared from RNA derived from a biological tissue of a subject according to a conventional method, and a pair of primers of the present invention (consisting of a sense strand and an antisense strand that bind to the above cDNA) is hybridized with the cDNA so that the region of each target gene can be amplified, and the PCR method is performed by a conventional method, and a method of detecting the obtained double-stranded DNA can be exemplified. As a method for detecting double-stranded DNA, a method using primers previously labeled with a radioisotope or a fluorescent substance for the above PCR, a method of electrophoresing a PCR product on an agarose gel and staining and detecting double-stranded DNA with ethidium bromide or the like, and a method of transferring the produced double-stranded DNA to a nylon membrane or the like according to a conventional method and hybridizing with a labeled nucleic acid probe for detection can be included.

[0573] When using nucleic acid array analysis, an RNA chip or a DNA chip with the nucleic acid probe (single-stranded or double-stranded) of the present invention attached to a substrate (solid phase) is used. The region where the nucleic acid probe is attached is called a probe spot, and the region where the nucleic acid probe is not attached is called a blank spot. Those in which a gene group is immobilized on a substrate are generally called nucleic acid chips, nucleic acid arrays, microarrays, etc. DNA or RNA arrays include DNA or RNA macroarrays and DNA or RNA microarrays. In this specification, when referring to a chip, it includes all of them. As the DNA chip, 3D-Gene (registered trademark) Human miRNA Oligo chip (Toray Industries, Inc.) can be used, but it is not limited thereto.

[0574] The measurement of the DNA chip is not limited, but for example, a method of detecting and measuring a signal derived from a labeling substance of a nucleic acid probe with an image detector (exemplified by Typhoon 9410 (GE Healthcare), 3D-Gene (registered trademark) scanner (Toray Industries, Inc.), etc.) can be exemplified.

[0575] As used herein, "stringent conditions" refer to conditions under which a nucleic acid probe hybridizes to its target sequence to a greater extent (e.g., a measurement value of at least the average of the background measurement value + 2 times the standard error of the background measurement value) than to other sequences.

[0576] Stringent conditions are defined by the conditions of hybridization and subsequent washing. The hybridization conditions include, but are not limited to, for example, conditions of 1 to 24 hours in a solution containing SSC, surfactant, formamide, dextran sulfate, blocking agent, etc. at 30°C to 60°C. Here, 1×SSC is an aqueous solution (pH 7.0) containing 150 mM sodium chloride and 15 mM sodium citrate, and the surfactant includes SDS (sodium dodecyl sulfate), Triton, or Tween, etc. More preferably, the hybridization conditions include 3 to 10×SSC and 0.1 to 1% SDS. Examples of the washing conditions after hybridization, which is another condition defining stringent conditions, include continuous washing with a solution containing 0.5×SSC and 0.1% SDS at 30°C, a solution containing 0.2×SSC and 0.1% SDS at 30°C, and a 0.05×SSC solution at 30°C. It is desirable that the complementary strand maintain a hybridized state with the target positive strand even when washed under such conditions. Specifically, such complementary strands include a strand consisting of a base sequence that is completely complementary to the base sequence of the target positive strand, and a strand consisting of a base sequence having at least 80%, preferably at least 85%, more preferably at least 90% or at least 95%, for example at least 98% or at least 99% identity with the said strand.

[0577] For other examples of "stringent conditions" in these hybridizations, see, for example, Sambrook, J. & Russel, D., Molecular Cloning, A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press, issued on January 15, 2001, Volume 1, Sections 7.42 - 7.45, Volume 2, Sections 8.9 - 8.17, etc., which can be used in the present invention.

[0578] Examples of conditions for performing PCR using the polynucleotide fragment in the kit of the present invention as a primer include, for example, using a PCR buffer having a composition such as 10 mM Tris - HCL (pH 8.3), 50 mM KCL, 1 - 2 mM MgCl2, and treating at about 15 seconds to 1 minute at a temperature of Tm value + 5 - 10 °C calculated from the sequence of the primer. Examples of the calculation method for such Tm value include Tm value = 2×(number of adenine residues + number of thymine residues) + 4×(number of guanine residues + number of cytosine residues).

[0579] Also, when using the quantitative RT - PCR method, commercially available measurement kits specially designed for quantitatively measuring miRNAs, such as TaqMan (registered trademark) MicroRNA Assays (Life Technologies), LNA (registered trademark) - based MicroRNA PCR (Exiqon), Ncode (registered trademark) miRNA qRT - PCT kit (invitrogen), etc., may be used.

[0580] For calculating the gene expression level, although not limited, for example, statistical processes described in "Statistical analysis of gene expression microarray data" (written by Speed T., Chapman and Hall / CRC), and "A beginner’s guide Microarray gene expression data analysis" (written by Causton H.C. et al., Blackwell publishing), etc. can be used in the present invention. For example, to the average value of the measured values of the blank spots on the DNA chip, add twice, preferably three times, more preferably six times the standard deviation of the measured values of the blank spots, and a probe spot having a signal value equal to or higher than that value can be regarded as a detection spot. Further, the average value of the measured values of the blank spots can be regarded as the background and subtracted from the measured value of the probe spot to obtain the gene expression level. For missing values of the gene expression level, they can be excluded from the analysis target, preferably replaced with the minimum value of the gene expression level in each DNA chip, more preferably replaced with a value obtained by subtracting 0.1 from the logarithmic value of the minimum value of the gene expression level. Further, in order to remove genes with low signals, only genes having a gene expression level of 2 to the 6th power, preferably 2 to the 8th power, more preferably 2 to the 10th power or higher in 20% or more, preferably 50% or more, more preferably 80% or more of the number of measurement samples can be selected as the analysis target. Examples of normalization of the gene expression level include, although not limited, global normalization and quantile n...

Claims

1. A kit for detecting colorectal cancer, comprising a nucleic acid probe that can specifically bind to a polynucleotide of miR-204-3p, which is a colorectal cancer marker, or its precursor, and / or a primer that specifically recognizes and amplifies the polynucleotide or its precursor.

2. The kit according to claim 1, wherein the nucleic acid probe or primer is selected from the group consisting of polynucleotides shown in the following (a) to (d): (a) A polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence, (b) A polynucleotide containing the nucleotide sequence represented by SEQ ID NO: 45, (c) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence, and (d) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence.

3. The kit includes another colorectal cancer marker, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p, miR-1227-5p, miR-6845-5p,miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, miR-24-3p, miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5p,The kit according to claim 1 or 2, further comprising at least one or more polynucleotides selected from the group consisting of miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, miR-6090, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085, miR-6752-5p and miR-135a-3p, or precursors thereof, and nucleic acid probes capable of specifically binding thereto, and / or primers capable of specifically recognizing and amplifying the polynucleotides or precursors thereof.

4. The kit according to claim 3, wherein the nucleic acid probe or primer is selected from the group consisting of polynucleotides shown in the following (e) to (h): (e) A polynucleotide consisting of the nucleotide sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614 or a nucleotide sequence in which u is t in the nucleotide sequence, (f) A polynucleotide containing the nucleotide sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, (g) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614 or a nucleotide sequence in which u is t in the nucleotide sequence, and (h) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614 or a nucleotide sequence in which u is t in the nucleotide sequence.

5. A method for assisting in the detection of colorectal cancer, comprising measuring the expression level of a target nucleic acid in a specimen of a subject using the kit according to any one of claims 1 to 4, and evaluating in vitro whether the subject has colorectal cancer or does not have colorectal cancer using the measured expression level and a control expression level of a healthy subject measured in the same manner.

6. The method according to claim 5, wherein the subject is a human.

7. The method according to claim 5 or 6, wherein the sample is blood, serum or plasma.

8. Use of a polynucleotide of miR-204-3p or a precursor thereof as a colorectal cancer marker for the detection of colorectal cancer.

9. The use according to claim 8, wherein the polynucleotide of miR-204-3p is a polynucleotide represented by any one of the following (a) or (b): (a) A polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 45, (b) A polynucleotide containing the nucleotide sequence represented by SEQ ID NO:

45.

10. The polypeptide of the miR-204-3p or its precursor is miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p, miR-1227-5p,miR-6845-5p, miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, miR-24-3p, miR-4697-5p, miR-3197, miR-675-5p, miR-4486Use according to claim 8 or 9, which is used as a colorectal cancer marker for the detection of colorectal cancer in combination with at least one or more polynucleotides selected from the group consisting of miR-7107-5p, miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, miR-6090, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085, miR-6752-5p and miR-135a-3p or precursors thereof.

11. The use according to claim 10, wherein the at least one polynucleotide is at least one selected from the group consisting of polynucleotides represented by any one of the following (i) and (j): (i) A polynucleotide consisting of the nucleotide sequence represented by any one of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, (j) A polynucleotide containing the nucleotide sequence represented by any one of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614.

12. Measuring the expression level of a target nucleic acid in a sample of a subject using a device for detecting colorectal cancer, which comprises a nucleic acid probe that can specifically bind to a polynucleotide of miR-204-3p or a precursor thereof as a colorectal cancer marker, and / or a primer that specifically recognizes and amplifies the polynucleotide or a precursor thereof, and evaluating in vitro whether the subject has colorectal cancer or does not have colorectal cancer using the measured expression level and a control expression level of a healthy subject measured in the same manner. A method for assisting in the detection of colorectal cancer.

13. The method according to claim 12, wherein the nucleic acid probe or primer is selected from the group consisting of polynucleotides represented by the following (a) to (d): (a) A polynucleotide consisting of the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence, (b) A polynucleotide containing the nucleotide sequence represented by SEQ ID NO: 45, (c) A polynucleotide consisting of a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence, and (d) A polynucleotide containing a nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 45 or a nucleotide sequence in which u is t in the nucleotide sequence.

14. The device is another colorectal cancer marker, miR-4257, miR-6787-5p, miR-6780b-5p, miR-3131, miR-7108-5p, miR-1343-3p, miR-1247-3p, miR-4651, miR-6757-5p, miR-3679-5p, miR-7641, miR-6746-5p, miR-8072, miR-6741-5p, miR-1908-5p, miR-6857-5p, miR-4746-3p, miR-744-5p, miR-4792, miR-564, miR-6791-5p, miR-6825-5p, miR-6826-5p, miR-4665-3p, miR-4467, miR-3188, miR-6125, miR-6756-5p, miR-1228-3p, miR-8063, miR-8069, miR-6875-5p, miR-3185, miR-4433b-3p, miR-6887-5p, miR-128-1-5p, miR-6724-5p, miR-1914-3p, miR-1225-5p, miR-4419b, miR-7110-5p, miR-187-5p, miR-3184-5p, miR-5572, miR-6729-5p, miR-615-5p, miR-6749-5p, miR-6515-3p, miR-6840-3p, miR-6893-5p, miR-4728-5p, miR-6717-5p, miR-7113-3p, miR-4665-5p, miR-642b-3p, miR-7109-5p, miR-6842-5p, miR-4442, miR-4433-3p, miR-4707-5p, miR-6126, miR-4449, miR-4706, miR-1913, miR-602, miR-939-5p, miR-4695-5p, miR-711, miR-6816-5p, miR-4632-5p, miR-6721-5p, miR-7847-3p, miR-6132, miR-887-3p, miR-3679-3p, miR-6784-5p, miR-1249, miR-937-5p, miR-5195-3p, miR-6732-5p, miR-4417, miR-4281, miR-4734, miR-6766-3p, miR-663a, miR-4513, miR-6781-5p, miR-1227-5p, miR-6845-5p,miR-6798-5p, miR-3620-5p, miR-1915-5p, miR-4294, miR-642a-3p, miR-371a-5p, miR-940, miR-4450, miR-4723-5p, miR-1469, miR-6861-5p, miR-7975, miR-6879-5p, miR-6802-5p, miR-1268b, miR-663b, miR-125a-3p, miR-2861, miR-6088, miR-4758-5p, miR-296-3p, miR-6738-5p, miR-671-5p, miR-4454, miR-4516, miR-7845-5p, miR-4741, miR-92b-5p, miR-6795-5p, miR-6805-3p, miR-4725-3p, miR-6782-5p, miR-4688, miR-6850-5p, miR-6777-5p, miR-6785-5p, miR-7106-5p, miR-3663-3p, miR-6131, miR-1915-3p, miR-4532, miR-6820-5p, miR-4689, miR-4638-5p, miR-3656, miR-3621, miR-6769b-5p, miR-149-3p, miR-23b-3p, miR-3135b, miR-6848-5p, miR-6769a-5p, miR-4327, miR-6765-3p, miR-6716-5p, miR-6877-5p, miR-6727-5p, miR-4534, miR-614, miR-1202, miR-575, miR-6870-5p, miR-6722-3p, miR-7977, miR-4649-5p, miR-4675, miR-6075, miR-6779-5p, miR-4271, miR-3196, miR-6803-5p, miR-6789-5p, miR-4648, miR-4508, miR-4749-5p, miR-4505, miR-5698, miR-1199-5p, miR-4763-3p, miR-1231, miR-1233-5p, miR-150-3p, miR-1225-3p, miR-92a-2-5p, miR-423-5p, miR-1268a, miR-128-2-5p, miR-24-3p, miR-4697-5p, miR-3197, miR-675-5p, miR-4486, miR-7107-5pThe method according to claim 12 or 13, further comprising a nucleic acid probe that can specifically bind to at least one or more polynucleotides selected from the group consisting of miR-23a-3p, miR-4667-5p, miR-451a, miR-3940-5p, miR-8059, miR-6813-5p, miR-4492, miR-4476, miR-6090, miR-6836-3p, miR-3195, miR-718, miR-3178, miR-638, miR-4497, miR-6085, miR-6752-5p, and miR-135a-3p or precursors thereof, and / or primers that specifically recognize and amplify the polynucleotide or precursors thereof.

15. The method according to claim 14, wherein the nucleic acid probe or primer is selected from the group consisting of polynucleotides shown in the following (e) to (h): (e) a polynucleotide consisting of a base sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, or a base sequence in which u is t in the base sequence, (f) a polynucleotide containing a base sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, (g) a polynucleotide consisting of a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, or a base sequence in which u is t in the base sequence, and (h) a polynucleotide containing a base sequence complementary to the base sequence represented by any of SEQ ID NOs: 2 to 44, 46 to 50, 52 to 194, and 606 to 614, or a base sequence in which u is t in the base sequence.

16. The method according to any one of claims 12 to 15, wherein the device is a device for measurement by a hybridization technique.

17. The method according to claim 16, wherein the hybridization technique is a nucleic acid array technique.

18. The method according to any one of claims 12 to 17, wherein the device is a chip or an array.

19. The method according to any one of claims 12 to 18, wherein the subject is a human.

20. The method according to any one of claims 12 to 19, wherein the sample is blood, serum or plasma.

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