Kit, device, and method for detecting bladder cancer
A miRNA-based kit for bladder cancer detection addresses the limitations of current methods by offering non-invasive and accurate diagnosis using a panel of specific microRNAs, enhancing sensitivity and specificity for early detection.
Patent Information
- Application Number
- JP2025145067
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2018-04-25
- Filing Date
- 2025-09-02
- Publication Date
- 2025-12-09
AI Technical Summary
Current diagnostic methods for bladder cancer, such as cystoscopy and urine cytology, suffer from low sensitivity and invasiveness, while existing protein and gene expression indicators have poor specificity and variability, leading to potential misdiagnosis and missed treatments.
A kit and device utilizing a set of specific microRNAs (miRNAs) as markers, including miR-1199-5p, miR-1225-5p, and others, for detecting bladder cancer from blood samples, allowing for non-invasive and accurate diagnosis using nucleic acid binding and expression level measurement.
The miRNA-based kit provides high sensitivity and specificity for bladder cancer detection, reducing the risk of misdiagnosis and improving patient outcomes by enabling early and accurate identification of the disease.
Smart Images

Figure 2025179134000126 
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Figure 2025179134000128
Abstract
Description
[Technical Field]
[0001] The present invention relates to a kit or device for detecting bladder cancer, which is used to test whether a subject is affected with bladder cancer and which contains a nucleic acid capable of specifically binding to a specific miRNA or its complementary strand, and a method for detecting bladder cancer, which comprises measuring the expression level of the miRNA. [Background technology]
[0002] The bladder is an organ located in the pelvis, and acts as a sort of bag where urine produced in the kidneys is temporarily stored after being transported via the renal pelvis and ureters. When the bladder is stretched by the accumulated urine, the urge to urinate is sensed, and the muscles contract to allow urination. The inner surface of the bladder is covered with transitional epithelial cells, which are highly elastic. Bladder cancer occurs when these transitional epithelial cells become cancerous, and histologically, transitional cell carcinoma is known to account for 90% of all bladder cancers.
[0003] The cancer mortality rate among Japanese people in 2008 was 547.7 per 100,000, and the proportion of bladder cancer deaths among these causes has been increasing year by year due to the aging population and the influence of Western culture. Bladder cancer and other urothelial cancers are the second most common urological tumors after prostate cancer. In Japan, the number of patients, primarily elderly, was approximately 16,000 in 2002, with the incidence rate being approximately four times higher in men than in women. Smoking is known to play a significant role in the development of bladder cancer, and occupational exposure to aromatic amines is also an established risk factor. Bladder cancer can be classified into three types by T factor in the TNM classification, which is used to assess the degree of invasiveness, or stage of disease: carcinoma in situ (Tis), superficial bladder cancer (Ta, T1), and invasive bladder cancer (T2 or higher), in descending order of invasiveness. Carcinoma in situ can occur in conjunction with superficial or invasive cancer, or it can occur alone. Because it can be scattered within the bladder mucosa or spread in a creeping manner, it can be easily overlooked even during endoscopic examination, a definitive test. Superficial bladder cancer is cancer that remains within the bladder surface, i.e., the superficial mucosa and the submucosa below it. While it rarely metastasizes to other organs, it tends to recur multiple times within the bladder, making follow-up examinations crucial. Invasive bladder cancer grows by spreading to the bladder muscle and outside the bladder, and is prone to metastasis. Bladder cancer is also graded as high or low histologically. High-grade bladder cancer is highly malignant and prone to early invasion and metastasis, making early detection particularly important.
[0004] Treatment for bladder cancer is determined based on the stage of progression (Japanese Urological Association, Japanese Society of Pathology, and Japanese Radiological Society, Guidelines for the Treatment of Renal Pelvis, Ureter, and Bladder Cancer, Kanehara Publishing, 2011), metastasis, and the patient's overall condition. Standard treatments for bladder cancer are outlined in the Japanese Urological Association / Bladder Cancer Clinical Practice Guidelines, 2015 Edition, Igaku Tosho Publishing). Currently, the most common treatments are surgical resection (transurethral resection of the bladder tumor (TUR-BT), radical cystectomy), radiation therapy, chemotherapy with anticancer drugs, and intravesical BCG therapy. Radical cystectomy is the standard treatment for invasive bladder cancer with TNM classification T2 or higher, and early detection is crucial.
[0005] Currently, the most reliable and common methods for detecting bladder cancer are cystoscopy and urine cytology. However, cystoscopy is highly invasive, and urine cytology, which detects exfoliated cancer cells microscopically, is the preferred method in terms of invasiveness. However, its specificity is reported to be approximately 94% and its sensitivity is reported to be 35% (Non-Patent Document 1).
[0006] Bladder cancer has a high recurrence rate, often occurring within two years. The recurrence rate after treatment is as high as 50-80%, and 10-25% of these cases are discovered as progressive, muscle-invasive cancer. Therefore, early detection and treatment of recurrence are important in order to extend patient survival.
[0007] Currently, several urinary protein markers are available as non-invasive clinical markers for bladder cancer. These marker tests have higher sensitivity than urinary cytology. For example, the NMP22 test, which detects the specific nuclear matrix protein NuMA, has a sensitivity of 47-100% and a specificity of 55-98% (Non-Patent Document 1). The BTAtrak test, which detects a specific basement membrane fragment complex, has a sensitivity of 60-83% and a specificity of 60-79% (Non-Patent Document 1).
[0008] Furthermore, markers that use gene expression as an indicator include miR-92a-2-5p, miR-150-3p, miR-1207-5p, miR-1202, miR-135a-3p, miR-1914-3p, miR-1469, miR-149-3p, and miR-663a shown in Patent Document 1, miR-1254, miR-1246, and miR-92a-3p shown in Patent Document 2, miR-191-5p and miR-940 shown in Non-Patent Document 2, and miR-423-5p shown in Non-Patent Document 3. [Prior art documents] [Patent documents]
[0009] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-000067 [Patent Document 2] U.S. Patent Application No. US2013 / 0084241 [Non-patent literature]
[0010] [Non-Patent Document 1] Bas WG van Rhijin et al., 2005, European Urology 47, p736-748 [Non-patent document 2] Long JD et al., 2015, Am J Transl Res 7(11)p2500-p2509 [Non-patent document 3] Du L et al., 2017, Oncotarget 8(25)p40832-p40842 Summary of the Invention [Problem to be solved by the invention]
[0011] Among the currently widely used diagnostic methods for bladder cancer, urinary cytology has a low sensitivity of 35%. This is due to the fact that sensitivity can vary depending on the type of specimen, such as the difficulty in distinguishing low grades of histological atypia, which are classified as high / low. Furthermore, high inter-observer variability means that it is not a universal test. While cystoscopy is said to have a high sensitivity of 90%, it is still subjective and often difficult to distinguish from mucosal inflammation. In cases of uncertainty, the follow-up period may be shortened and a decision may be deferred until the next cystoscopy, resulting in a diagnosis of cancer, raising the risk of overlooking the diagnosis. Furthermore, cystoscopy is performed transurethrally without anesthesia, which is painful for patients, especially men due to the presence of their penises, and places a burden on them through unnecessary testing. The existing protein and gene expression indicators mentioned above have drawbacks, such as poor specificity and / or sensitivity, and significant variability in measurement results depending on the timing of testing.
[0012] Therefore, there is a possibility that unnecessary additional tests will be performed due to the misidentification of non-bladder cancer patients as bladder cancer patients, and that treatment opportunities will be missed due to the overlooking of bladder cancer patients. Therefore, there is a strong need for a highly accurate marker that can accurately distinguish bladder cancer regardless of stage, degree of invasion, histological atypia, or primary / recurrent status. In addition, Patent Document 1 describes a method for detecting bladder cancer from urine samples, and it states that the accuracy was 86% for a validation group of 36 cases (27 of which were bladder cancer cases). However, the number of validation samples was insufficient, and the amount of nucleic acid in urine is very low, so a large amount of urine is required, making the detection process complicated and not yet practical.
[0013] An object of the present invention is to provide a disease diagnostic kit or device useful for diagnosing and treating bladder cancer non-invasively and with a small amount of sample, and a method for determining (or detecting) bladder cancer. [Means for solving the problem]
[0014] As a result of intensive research to solve the above problems, the inventors discovered a gene that can be used as a marker for detecting bladder cancer from blood, which can be collected minimally invasively, and found that this gene can be used to significantly detect bladder cancer, thereby completing the present invention.
[0015] <Summary of the Invention> That is, the present invention includes the following aspects. (1) iR-1199-5p、miR-1225-5p、miR-1227-5p、miR-1228-3p、miR-1228-5p、miR -1237-5p、miR-1238-5p、miR-1247-3p、miR-1268a、miR-1268b、miR-1273g -3p、miR-128-2-5p、miR-1343-3p、miR-1343-5p、miR-1470、miR-17-3p、mi R-187-5p、miR-1908-3p、miR-1908-5p、miR-1909-3p、miR-1915-3p、miR-2 10-5p、miR-24-3p、miR-2467-3p、miR-2861、miR-296-3p、miR-29b-3p、miR -3131、miR-3154、miR-3158-5p、miR-3160-5p、miR-3162-5p、miR-3178、mi R-3180-3p、miR-3184-5p、miR-3185、miR-3194-3p、miR-3195、miR-3197、m iR-320a、miR-320b、miR-328-5p、miR-342-5p、miR-345-3p、miR-3616-3p、 miR-3619-3p、miR-3620-5p、miR-3621、miR-3622a-5p、miR-3648、miR-365 2、miR-3656、miR-3663-3p、miR-3679-5p、miR-371b-5p、miR-373-5p、miR- 3917、miR-3940-5p、miR-3960、miR-4258、miR-4259、miR-4270、miR-4286、 miR-4298、miR-4322、miR-4327、miR-4417、miR-4419b、miR-4429、miR-443 0、miR-4433a-3p、miR-4436b-5p、miR-4443、miR-4446-3p、miR-4447、miR- 4448、miR-4449、miR-4454、miR-4455、miR-4459、miR-4462、miR-4466、miR -4467、miR-4480、miR-4483、miR-4484、miR-4485-5p、miR-4488、miR-4492、miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, m iR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, m iR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-49 8, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131 miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR- 6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760 -5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5pmiR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p , miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5 p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836- 3p, miR-6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870 A kit for detecting bladder cancer, comprising at least one polynucleotide selected from miR-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, and miR-937-5p, or a nucleic acid capable of specifically binding to a complementary strand of the polynucleotide.
[0016] (2) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228 or a nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence complementary to the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The kit according to (1), wherein the polynucleotide is selected from the group consisting of:
[0017] (3) The kit according to (1) or (2), further comprising at least one polynucleotide selected from another bladder cancer marker, miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940, or a nucleic acid capable of specifically binding to a complementary strand of the polynucleotide.
[0018] (4) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 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 comprising a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243 or the nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The kit according to (3), wherein the polynucleotide is selected from the group consisting of:
[0019] (5) iR-1199-5p、miR-1225-5p、miR-1227-5p、miR-1228-3p、miR-1228-5p、miR -1237-5p、miR-1238-5p、miR-1247-3p、miR-1268a、miR-1268b、miR-1273g -3p、miR-128-2-5p、miR-1343-3p、miR-1343-5p、miR-1470、miR-17-3p、mi R-187-5p、miR-1908-3p、miR-1908-5p、miR-1909-3p、miR-1915-3p、miR-2 10-5p、miR-24-3p、miR-2467-3p、miR-2861、miR-296-3p、miR-29b-3p、miR -3131、miR-3154、miR-3158-5p、miR-3160-5p、miR-3162-5p、miR-3178、mi R-3180-3p、miR-3184-5p、miR-3185、miR-3194-3p、miR-3195、miR-3197、m iR-320a、miR-320b、miR-328-5p、miR-342-5p、miR-345-3p、miR-3616-3p、 miR-3619-3p、miR-3620-5p、miR-3621、miR-3622a-5p、miR-3648、miR-365 2、miR-3656、miR-3663-3p、miR-3679-5p、miR-371b-5p、miR-373-5p、miR- 3917、miR-3940-5p、miR-3960、miR-4258、miR-4259、miR-4270、miR-4286、 miR-4298、miR-4322、miR-4327、miR-4417、miR-4419b、miR-4429、miR-443 0、miR-4433a-3p、miR-4436b-5p、miR-4443、miR-4446-3p、miR-4447、miR- 4448、miR-4449、miR-4454、miR-4455、miR-4459、miR-4462、miR-4466、miR -4467、miR-4480、miR-4483、miR-4484、miR-4485-5p、miR-4488、miR-4492、miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, m iR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, m iR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-49 8, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131 miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR- 6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760 -5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5pmiR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p , miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5 p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836- 3p, miR-6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870- A device for detecting bladder cancer, comprising at least one polynucleotide selected from miR-6877-5p, miR-6879-5p, miR-6880-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, and miR-937-5p, or a nucleic acid capable of specifically binding to a complementary strand of the polynucleotide.
[0020] (6) The nucleic acid is a polynucleotide represented by any one of the following (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228 or a nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence complementary to the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The device according to (5), wherein the polynucleotide is selected from the group consisting of:
[0021] (7) The device according to (5) or (6), further comprising at least one polynucleotide selected from another bladder cancer marker, miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940, or a nucleic acid capable of specifically binding to a complementary strand of the polynucleotide.
[0022] (8) The nucleic acid is a polynucleotide represented by any one of the following (f) to (j): (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 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 comprising a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243 or the nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The device according to (7), wherein the polynucleotide is selected from the group consisting of:
[0023] (9) The device according to any one of (5) to (8), which is a device for measurement by hybridization technology.
[0024] (10) The device according to (9), wherein the hybridization technology is a nucleic acid array technology.
[0025] (11) p、miR-1193、miR-1199-5p、miR-1225-5p、miR-1227-5p、miR-1228-3p、miR -1228-5p、miR-1237-5p、miR-1238-5p、miR-1247-3p、miR-1268a、miR-126 8b、miR-1273g-3p、miR-128-2-5p、miR-1343-3p、miR-1343-5p、miR-1470、m iR-17-3p、miR-187-5p、miR-1908-3p、miR-1908-5p、miR-1909-3p、miR-19 15-3p、miR-210-5p、miR-24-3p、miR-2467-3p、miR-2861、miR-296-3p、miR -29b-3p、miR-3131、miR-3154、miR-3158-5p、miR-3160-5p、miR-3162-5p、 miR-3178、miR-3180-3p、miR-3184-5p、miR-3185、miR-3194-3p、miR-3195、 miR-3197、miR-320a、miR-320b、miR-328-5p、miR-342-5p、miR-345-3p、mi R-3616-3p、miR-3619-3p、miR-3620-5p、miR-3621、miR-3622a-5p、miR-36 48、miR-3652、miR-3656、miR-3663-3p、miR-3679-5p、miR-371b-5p、miR-3 73-5p、miR-3917、miR-3940-5p、miR-3960、miR-4258、miR-4259、miR-4270、 miR-4286、miR-4298、miR-4322、miR-4327、miR-4417、miR-4419b、miR-442 9、miR-4430、miR-4433a-3p、miR-4436b-5p、miR-4443、miR-4446-3p、miR- 4447、miR-4448、miR-4449、miR-4454、miR-4455、miR-4459、miR-4462、miR -4466、miR-4467、miR-4480、miR-4483、miR-4484、miR-4485-5p、miR-4488、miR-4492, miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR- 4655-5p, miR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, mi R-4707-3p, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p miR-4736, miR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR- 4792, miR-498, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-612 4, miR-6131, miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR- 6716-5p, miR-6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749 -5p、miR-6760-5p、miR-6762-5p、miR-6765-3p、miR-6765-5p、miR-6766-3p、miR-6766-5p、miR-6771-5p、miR-6774-5p、miR-6777-5p、miR-6778-5p、miR-6780b-5p, miR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p , miR-6789-5p, miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, m The expression level of at least one polynucleotide selected from iR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, and miR-937-5p is measured, and the presence or absence of bladder cancer in a subject is determined using the measured expression level. A method for detecting bladder cancer, comprising evaluating in vitro.
[0026] (12) The method according to (11), comprising substituting the expression level of the at least one polynucleotide in a sample derived from a subject known to have bladder cancer and the gene expression level of a sample derived from a subject not suffering from bladder cancer into a discriminant that is capable of discriminating between the presence or absence of bladder cancer, and thereby assessing the presence or absence of bladder cancer.
[0027] (13) The expression level of the polynucleotide is measured using a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is a polynucleotide shown in any one of the following (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228 or a nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence complementary to the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The method according to (11) or (12), wherein the polynucleotide is selected from the group consisting of:
[0028] (14) The method according to any one of (11) to (13), further comprising measuring the expression level of at least one polynucleotide selected from other bladder cancer markers: miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940.
[0029] (15) The expression level of the polynucleotide is measured using a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is a polynucleotide shown in any one of the following (f) to (j): (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 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 comprising a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243 or the nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The method according to (14), wherein the polynucleotide is selected from the group consisting of:
[0030] (16) The method according to any one of (11) to (15), wherein the expression level of a target gene in a sample from a subject is measured using the kit according to any one of (1) to (4) or the device according to any one of (5) to (10), which contains a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide.
[0031] (17) The method according to any one of (11) to (16), wherein the subject is a human.
[0032] (18) The method according to any one of (11) to (17), wherein the sample is blood, serum, or plasma.
[0033] <Terminology> Terms used herein have the following definitions. The abbreviations for nucleotide, polynucleotide, DNA, RNA, etc. shall be in accordance with the "Guidelines for the Preparation of Specifications Including Nucleotide Sequences or Amino Acid Sequences" (edited by the Japan Patent Office) and common practice in the technical field.
[0034] As used herein, the term "polynucleotide" refers to nucleic acids, including RNA, DNA, and RNA / DNA chimeras. The term "DNA" includes cDNA, genomic DNA, and synthetic DNA. The term "RNA" includes 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 using, for example, an automated nucleic acid synthesizer, based on a predetermined base sequence (which may be either a natural or non-natural sequence). As used herein, the term "non-natural sequence" is intended to be used in a broad sense and includes sequences that differ from a natural sequence, such as sequences containing one or more nucleotide substitutions, deletions, insertions, and / or additions (i.e., mutant sequences), sequences containing one or more modified nucleotides (i.e., modified sequences), and the like. As used herein, the term "polynucleotide" is used interchangeably with the term "nucleic acid."
[0035] As used herein, a "fragment" refers to a polynucleotide having a continuous partial base sequence of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, and more preferably 19 bases or more.
[0036] As used herein, the term "gene" is intended to encompass not only RNA and double-stranded DNA, but also each of the single-stranded DNAs that constitute them, such as the positive strand (or sense strand) or complementary strand (or antisense strand), and is not particularly limited by its length.
[0037] Therefore, unless otherwise specified, the term "gene" as used herein includes double-stranded DNA, including human genomic DNA, single-stranded DNA (positive strand), single-stranded DNA (complementary strand) having a sequence complementary to the positive strand, cDNA, microRNA (miRNA), and fragments thereof, the human genome, and transcription products thereof. Furthermore, the term "gene" encompasses not only "genes" represented by specific nucleotide sequences (or SEQ ID NO: 1), but also "nucleic acids" encoding RNAs with biological functions equivalent to the RNAs encoded by these sequences, such as homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Specific examples of "nucleic acids" encoding such homologs, variants, or derivatives include "nucleic acids" having a nucleotide sequence that hybridizes under stringent conditions to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 766 or the complementary sequence of the nucleotide sequence in which "u" is replaced by "t" in the nucleotide sequence. The term "gene" does not limit the scope of functional regions, and may include, for example, expression control regions, coding regions, exons, or introns. Furthermore, the "gene" may be contained within the cell, may be released outside the cell and exist independently, or may be encapsulated in a vesicle called an exosome.
[0038] As used herein, "exosomes" or "exosomes" refer to vesicles enclosed in a lipid bilayer membrane that are secreted from cells. Exosomes are derived from multivesicular endosomes and, when released into the extracellular environment, may contain biological substances such as RNA, DNA, and other "genes" and proteins. Exosomes are known to be contained in body fluids such as blood, serum, plasma, serum, and lymph.
[0039] As used herein, the term "transcription product" refers to RNA synthesized using the DNA sequence of a gene as a template. RNA polymerase binds to a site called the promoter located upstream of the gene, and RNA is synthesized by attaching ribonucleotides to the 3' end so that the sequence is complementary to the DNA base sequence. This RNA includes not only the gene itself, but also the entire sequence from the transcription start point to the end of the poly(A) sequence, including expression control regions, coding regions, exons, and introns.
[0040] Furthermore, unless otherwise specified, the term "microRNA (miRNA)" as used herein refers to a 15-25 base non-coding RNA that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleaving enzyme with RNase III cleavage activity, incorporated into a protein complex called RISC, and involved in the translational repression of mRNA. Furthermore, the term "miRNA" as used herein not only refers to a "miRNA" represented by a specific base sequence (or SEQ ID NO:), but also encompasses "miRNA" that contains a precursor of the "miRNA" (pre-miRNA, pri-miRNA) and has biological functions equivalent to those of the miRNA encoded by these, such as homologs (i.e., homologs or orthologs), variants such as genetic polymorphisms, and derivatives. Specific examples of "miRNAs" encoding such precursors, homologs, mutants, or derivatives can be identified using miRBase release 21 (http: / / www.mirbase.org / ), and include "miRNAs" having a nucleotide sequence that hybridizes under stringent conditions described below with the complementary sequence of any of the specific nucleotide sequences represented by SEQ ID NOs: 1 to 766. Furthermore, as used herein, "miRNA" may refer to the gene product of a miR gene, and such gene products include mature miRNAs (e.g., non-coding RNAs of 15 to 25 bases or 19 to 25 bases involved in translational repression of mRNA as described above) or miRNA precursors (e.g., pre-miRNAs or pri-miRNAs as described above).
[0041] As used herein, the term "probe" encompasses a polynucleotide used to specifically detect RNA produced by gene expression or a polynucleotide derived therefrom, and / or a polynucleotide complementary thereto.
[0042] As used herein, the term "primer" encompasses consecutive polynucleotides and / or polynucleotides complementary thereto that specifically recognize and amplify RNA produced by gene expression or a polynucleotide derived therefrom.
[0043] Here, a complementary polynucleotide (complementary strand, reverse strand) refers to a polynucleotide that is base-complementary to the full-length sequence of a polynucleotide consisting of a base sequence defined by any one of SEQ ID NOS: 1 to 766 or a base sequence in which u is t in that base sequence, or a partial sequence thereof (herein referred to as the positive strand for convenience), based on base pairing such as A:T(U) or G:C. However, such a complementary strand is not limited to forming a completely complementary sequence with the base sequence of the target positive strand, and may have a complementary relationship to the extent that it can hybridize with the target positive strand under stringent conditions.
[0044] As used herein, "stringent conditions" refers to conditions under which a nucleic acid probe hybridizes to its target sequence to a detectably greater extent (e.g., a measurement value of at least the mean of background measurements plus twice the standard error of the background measurement) than to other sequences. Stringent conditions are sequence-dependent and vary depending on the environment in which hybridization occurs. By controlling the stringency of hybridization and / or washing conditions, a target sequence that is 100% complementary to a nucleic acid probe can be identified. Specific examples of "stringent conditions" are described below.
[0045] As used herein, the term "Tm value" refers to the temperature at which the double-stranded portion of a polynucleotide is denatured into a single strand, and the double strand and single strand exist in a 1:1 ratio.
[0046] As used herein, the term "variant" refers, in the case of nucleic acids, to natural variants resulting from polymorphism, mutation, etc., or variants containing deletion, substitution, addition, or insertion of one, two, three, or more (e.g., one to several) bases in a base sequence represented by a SEQ ID NO: or in the base sequence where u is t, or a partial sequence thereof; or variants containing deletion, substitution, addition, or insertion of one or more bases in a base sequence of a precursor RNA (premature miRNA) of any of SEQ ID NOs: 1 to 243, or in the base sequence where u is t, or a partial sequence thereof; or variants showing about 90% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more percent identity with each of the base sequences or their partial sequences; or nucleic acids that hybridize to a polynucleotide or oligonucleotide containing the base sequence or its partial sequence under stringent conditions as defined above.
[0047] As used herein, "several" means an integer of about 10, 9, 8, 7, 6, 5, 4, 3, or 2.
[0048] As used herein, mutants can be prepared using well-known techniques such as site-directed mutagenesis and PCR-based mutagenesis.
[0049] As used herein, "% identity" can be determined using a protein or gene search system such as BLAST (https: / / blast.ncbi.nlm.nih.gov / Blast.cgi) or FASTA (http: / / www.genome.jp / tools / fasta / ), with or without introducing gaps (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7, pp. 203-214; Altschul, S. F. et al., 1990, Journal of Molecular Biology, Vol. 215, pp. 403-410; Pearson, W. R. et al., 1988, Proc. Natl. Acad. Sci. USA, Vol. 85, pp. 2444-2448).
[0050] As used herein, the term "derivative" includes, but is not limited to, modified nucleic acids, derivatives labeled with, for example, a fluorophore, derivatives containing modified nucleotides (e.g., nucleotides containing groups such as halogen, alkyl such as methyl, alkoxy such as methoxy, thio, and carboxymethyl, and nucleotides that have undergone base rearrangement, double bond saturation, deamination, or substitution of oxygen molecules with sulfur molecules), PNA (peptide nucleic acid; Nielsen, P.E. et al., 1991, Science, Vol. 254, pp. 1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., Vol. 39, pp. 5401-5404), and the like.
[0051] As used herein, a "nucleic acid" capable of specifically binding to a polynucleotide selected from the miRNAs that are bladder cancer markers, or a complementary strand of the polynucleotide, refers to a synthetic or prepared nucleic acid, specifically including a "nucleic acid probe" or "primer," which is used directly or indirectly to detect the presence or absence of bladder cancer in a subject, to diagnose the presence or absence of bladder cancer, the severity of bladder cancer, the presence or degree of improvement of bladder cancer, or sensitivity to bladder cancer treatment, or to screen for candidate substances useful for preventing, ameliorating, or treating bladder cancer. These include nucleotides, oligonucleotides, and polynucleotides capable of specifically recognizing and binding to a transcription product represented by any of SEQ ID NOS: 1 to 766 or a cDNA synthetic nucleic acid thereof, or a complementary strand thereof, in a biological sample, particularly a body fluid such as blood or urine, in relation to bladder cancer. Based on the above-described properties, these nucleotides, oligonucleotides, and polynucleotides can be effectively used as probes for detecting the gene expressed in vivo, in tissues, cells, etc., or as primers for amplifying the gene expressed in vivo.
[0052] The term "detection" as used herein may be replaced with the terms "test," "measurement," "detection," or "assistance in diagnosis." Furthermore, the term "evaluation" as used herein is used to include the support of diagnosis or assessment based on test results or measurement results.
[0053] As used herein, "subject" refers to mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep and goats, rodents such as mice and rats, and animals kept in zoos. A preferred subject is a human. A "healthy subject" also refers to such a mammal that is not affected by the cancer to be detected. A preferred healthy subject is a human.
[0054] As used herein, "bladder cancer" refers to a malignant tumor that occurs in the bladder, and also includes urothelial cancer, which includes the renal pelvis and ureter.
[0055] As used herein, "P" or "P value" indicates the probability that a statistical value that is more extreme than the statistical value actually calculated from data under the null hypothesis will be observed in a statistical test. Therefore, the smaller the "P" or "P value," the more significant the difference between the compared subjects.
[0056] As used herein, "sensitivity" refers to the value of (the number of true positives) / (the number of true positives + the number of false negatives). High sensitivity enables early detection of bladder cancer, leading to complete resection of cancerous tissue and a reduced recurrence rate.
[0057] As used herein, "specificity" means (number of true negatives) / (number of true negatives + number of false positives). High specificity prevents unnecessary additional testing due to misidentification of healthy individuals as bladder cancer patients, reducing the burden on patients and medical costs.
[0058] In this specification, "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 samples, and is the primary index for evaluating detection performance.
[0059] As used herein, the term "specimen" to be assessed, detected, or diagnosed refers to tissues and biological materials in which the expression of the gene of the present invention changes with the onset, progression, and therapeutic effects of bladder cancer. Specifically, this refers to bladder tissue, renal pelvis, ureter, lymph nodes, and surrounding organs, as well as organs suspected of metastasis, skin, and bodily fluids such as blood, urine, saliva, sweat, and tissue exudates, as well as serum and plasma prepared from blood, feces, and hair. It also refers to biological samples extracted from these, specifically genes such as RNA and miRNA.
[0060] As used herein, the term "hsa-miR-6087 gene" or "hsa-miR-6087" encompasses the hsa-miR-6087 gene set forth in SEQ ID NO: 1 (miRBase Accession No. MIMAT0023712) as well as homologs or orthologs from other biological species. The gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev., Vol. 21, pp. 2049-2057. Furthermore, a known precursor of "hsa-miR-6087" is "hsa-mir-6087" (miRBase Accession No. MI0020364, SEQ ID NO: 244), which has a hairpin-like structure.
[0061] As used herein, the terms "hsa-miR-1185-1-3p gene" or "hsa-miR-1185-1-3p" encompass the hsa-miR-1185-1-3p gene set forth in SEQ ID NO: 2 (miRBase Accession No. MIMAT0022838) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., vol. 16, pp. 1289-1298. Furthermore, "hsa-miR-1185-1-3p" is known to have a precursor, "hsa-mir-1185-1" (miRBase Accession No. MI0003844, SEQ ID NO: 245), which has a hairpin-like structure.
[0062] As used herein, the term "hsa-miR-1185-2-3p gene" or "hsa-miR-1185-2-3p" encompasses the hsa-miR-1185-2-3p gene set forth in SEQ ID NO: 3 (miRBase Accession No. MIMAT0022713) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., 16, 1289-1298. Furthermore, "hsa-miR-1185-2-3p" is known to have a precursor, "hsa-mir-1185-2" (miRBase Accession No. MI0003821, SEQ ID NO: 246), which has a hairpin-like structure.
[0063] As used herein, the term "hsa-miR-1193 gene" or "hsa-miR-1193" encompasses the hsa-miR-1193 gene set forth in SEQ ID NO: 4 (miRBase Accession No. MIMAT0015049) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, a known precursor of "hsa-miR-1193" is "hsa-mir-1193" (miRBase Accession No. MI0014205, SEQ ID NO: 247), which has a hairpin-like structure.
[0064] As used herein, the terms "hsa-miR-1199-5p gene" or "hsa-miR-1199-5p" encompass the hsa-miR-1199-5p gene set forth in SEQ ID NO: 5 (miRBase Accession No. MIMAT0031119) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Salvi A et al., 2013, Int J Oncol., vol. 42, pp. 391-402. Furthermore, "hsa-miR-1199-5p" is known to have a precursor, "hsa-mir-1199" (miRBase Accession No. MI0020340, SEQ ID NO: 248), which has a hairpin-like structure.
[0065] As used herein, the terms "hsa-miR-1225-5p gene" or "hsa-miR-1225-5p" encompass the hsa-miR-1225-5p gene set forth in SEQ ID NO: 6 (miRBase Accession No. MIMAT0005572) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, "hsa-miR-1225-5p" is known to have a precursor, "hsa-mir-1225" (miRBase Accession No. MI0006311, SEQ ID NO: 249), which has a hairpin-like structure.
[0066] As used herein, the terms "hsa-miR-1227-5p gene" or "hsa-miR-1227-5p" encompass the hsa-miR-1227-5p gene set forth in SEQ ID NO: 7 (miRBase Accession No. MIMAT0022941) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, the precursor of "hsa-miR-1227-5p" is known to be "hsa-mir-1227" (miRBase Accession No. MI0006316, SEQ ID NO: 250), which has a hairpin-like structure.
[0067] As used herein, the terms "hsa-miR-1228-3p gene" or "hsa-miR-1228-3p" encompass the hsa-miR-1228-3p gene set forth in SEQ ID NO: 8 (miRBase Accession No. MIMAT0005583) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, the precursor of "hsa-miR-1228-3p" is known to be "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 251), which has a hairpin-like structure.
[0068] As used herein, the terms "hsa-miR-1228-5p gene" or "hsa-miR-1228-5p" encompass the hsa-miR-1228-5p gene set forth in SEQ ID NO: 9 (miRBase Accession No. MIMAT0005582) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, the precursor of "hsa-miR-1228-5p" is known to be "hsa-mir-1228" (miRBase Accession No. MI0006318, SEQ ID NO: 252), which has a hairpin-like structure.
[0069] As used herein, the terms "hsa-miR-1237-5p gene" or "hsa-miR-1237-5p" encompass the hsa-miR-1237-5p gene set forth in SEQ ID NO: 10 (miRBase Accession No. MIMAT0022946) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, the precursor of "hsa-miR-1237-5p" is known to be "hsa-mir-1237" (miRBase Accession No. MI0006327, SEQ ID NO: 253), which has a hairpin-like structure.
[0070] As used herein, the terms "hsa-miR-1238-5p gene" or "hsa-miR-1238-5p" encompass the hsa-miR-1238-5p gene set forth in SEQ ID NO: 11 (miRBase Accession No. MIMAT0022947) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell., 28, 328-336. Furthermore, "hsa-miR-1238-5p" is known to have a precursor, "hsa-mir-1238" (miRBase Accession No. MI0006328, SEQ ID NO: 254), which has a hairpin-like structure.
[0071] As used herein, the terms "hsa-miR-1247-3p gene" or "hsa-miR-1247-3p" encompass the hsa-miR-1247-3p gene set forth in SEQ ID NO: 12 (miRBase Accession No. MIMAT0022721) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res., vol. 18, pp. 610-621. Furthermore, the precursor of "hsa-miR-1247-3p" is known to be "hsa-mir-1247" (miRBase Accession No. MI0006382, SEQ ID NO: 255), which has a hairpin-like structure.
[0072] As used herein, the term "hsa-miR-1268a gene" or "hsa-miR-1268a" encompasses the hsa-miR-1268a gene set forth in SEQ ID NO: 13 (miRBase Accession No. MIMAT0005922) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res., vol. 18, pp. 610-621. Furthermore, "hsa-miR-1268a" is known to have a precursor, "hsa-mir-1268a" (miRBase Accession No. MI0006405, SEQ ID NO: 256), which has a hairpin-like structure.
[0073] As used herein, the term "hsa-miR-1268b gene" or "hsa-miR-1268b" encompasses the hsa-miR-1268b gene set forth in SEQ ID NO: 14 (miRBase Accession No. MIMAT0018925) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-1268b" is known to have a precursor, "hsa-mir-1268b" (miRBase Accession No. MI0016748, SEQ ID NO: 257), which has a hairpin-like structure.
[0074] As used herein, the terms "hsa-miR-1273g-3p gene" or "hsa-miR-1273g-3p" encompass the hsa-miR-1273g-3p gene set forth in SEQ ID NO: 15 (miRBase Accession No. MIMAT0022742) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Reshmi G et al., 2011, Genomics., 97, 333-340. Furthermore, the precursor of "hsa-miR-1273g-3p" is known to be "hsa-mir-1273g" (miRBase Accession No. MI0018003, SEQ ID NO: 258), which has a hairpin-like structure.
[0075] As used herein, the terms "hsa-miR-128-2-5p gene" or "hsa-miR-128-2-5p" encompass the hsa-miR-128-2-5p gene set forth in SEQ ID NO: 16 (miRBase Accession No. MIMAT0031095) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr. Biol., 12, 735-739. Furthermore, the precursor of "hsa-miR-128-2-5p" is known to be "hsa-mir-128-2" (miRBase Accession No. MI0000727, SEQ ID NO: 259), which has a hairpin-like structure.
[0076] As used herein, the terms "hsa-miR-1343-3p gene" or "hsa-miR-1343-3p" encompass the hsa-miR-1343-3p gene set forth in SEQ ID NO: 17 (miRBase Accession No. MIMAT0019776) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-1343-3p" is known to be "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 260), which has a hairpin-like structure.
[0077] As used herein, the terms "hsa-miR-1343-5p gene" or "hsa-miR-1343-5p" encompass the hsa-miR-1343-5p gene set forth in SEQ ID NO: 18 (miRBase Accession No. MIMAT0027038) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-1343-5p" is known to be "hsa-mir-1343" (miRBase Accession No. MI0017320, SEQ ID NO: 261), which has a hairpin-like structure.
[0078] As used herein, the term "hsa-miR-1470 gene" or "hsa-miR-1470" encompasses the hsa-miR-1470 gene set forth in SEQ ID NO: 19 (miRBase Accession No. MIMAT0007348) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, 9, 157. Furthermore, a known precursor of "hsa-miR-1470" is "hsa-mir-1470" (miRBase Accession No. MI0007075, SEQ ID NO: 262), which has a hairpin-like structure.
[0079] As used herein, the term "hsa-miR-17-3p gene" or "hsa-miR-17-3p" encompasses the hsa-miR-17-3p gene set forth in SEQ ID NO: 20 (miRBase Accession No. MIMAT0000071) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science., vol. 294, pp. 853-858. It is also known that the precursor of "hsa-miR-17-3p" is "hsa-mir-17" (miRBase Accession No. MI0000071, SEQ ID NO: 263), which has a hairpin-like structure.
[0080] As used herein, the terms "hsa-miR-187-5p gene" or "hsa-miR-187-5p" encompass the hsa-miR-187-5p gene set forth in SEQ ID NO: 21 (miRBase Accession No. MIMAT0004561) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Lim LP et al., 2003, Science., vol. 299, p. 1540. Furthermore, "hsa-miR-187-5p" is known to have a precursor, "hsa-mir-187" (miRBase Accession No. MI0000274, SEQ ID NO: 264), which has a hairpin-like structure.
[0081] As used herein, the terms "hsa-miR-1908-3p gene" or "hsa-miR-1908-3p" encompass the hsa-miR-1908-3p gene set forth in SEQ ID NO: 22 (miRBase Accession No. MIMAT0026916) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. Furthermore, the precursor of "hsa-miR-1908-3p" is known to be "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 265), which has a hairpin-like structure.
[0082] As used herein, the terms "hsa-miR-1908-5p gene" or "hsa-miR-1908-5p" encompass the hsa-miR-1908-5p gene set forth in SEQ ID NO: 23 (miRBase Accession No. MIMAT0007881) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells, vol. 26, pp. 2496-2505. Furthermore, "hsa-miR-1908-5p" is known to have a precursor, "hsa-mir-1908" (miRBase Accession No. MI0008329, SEQ ID NO: 266), which has a hairpin-like structure.
[0083] As used herein, the terms "hsa-miR-1909-3p gene" or "hsa-miR-1909-3p" encompass the hsa-miR-1909-3p gene set forth in SEQ ID NO: 24 (miRBase Accession No. MIMAT0007883) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells., vol. 26, pp. 2496-2505. It is also known that the precursor of "hsa-miR-1909-3p" is "hsa-mir-1909" (miRBase Accession No. MI0008330, SEQ ID NO: 267), which has a hairpin-like structure.
[0084] As used herein, the terms "hsa-miR-1915-3p gene" or "hsa-miR-1915-3p" encompass the hsa-miR-1915-3p gene set forth in SEQ ID NO: 25 (miRBase Accession No. MIMAT0007892) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells., vol. 26, pp. 2496-2505. Furthermore, the precursor of "hsa-miR-1915-3p" is known to be "hsa-mir-1915" (miRBase Accession No. MI0008336, SEQ ID NO: 268), which has a hairpin-like structure.
[0085] As used herein, the terms "hsa-miR-210-5p gene" or "hsa-miR-210-5p" encompass the hsa-miR-210-5p gene set forth in SEQ ID NO: 26 (miRBase Accession No. MIMAT0026475) and homologs or orthologs from other species. The gene can be obtained by the method described in Lim LP et al., 2003, Science., vol. 299, p. 1540. It is also known that the precursor of "hsa-miR-210-5p" is "hsa-mir-210" (miRBase Accession No. MI0000286, SEQ ID NO: 269), which has a hairpin-like structure.
[0086] As used herein, the term "hsa-miR-24-3p gene" or "hsa-miR-24-3p" encompasses the hsa-miR-24-3p gene set forth in SEQ ID NO: 27 (miRBase Accession No. MIMAT0000080) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2001, Science., vol. 294, pp. 853-858. Furthermore, known precursors of "hsa-miR-24-3p" are "hsa-mir-24-1" (miRBase Accession No. MI0000080, SEQ ID NO: 472) and "hsa-mir-24-2" (miRBase Accession No. MI0000081, SEQ ID NO: 484), which have a hairpin-like structure.
[0087] As used herein, the terms "hsa-miR-2467-3p gene" or "hsa-miR-2467-3p" encompass the hsa-miR-2467-3p gene set forth in SEQ ID NO: 28 (miRBase Accession No. MIMAT0019953) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-2467-3p" is known to be "hsa-mir-2467" (miRBase Accession No. MI0017432, SEQ ID NO: 270), which has a hairpin-like structure.
[0088] As used herein, the term "hsa-miR-2861 gene" or "hsa-miR-2861" encompasses the hsa-miR-2861 gene set forth in SEQ ID NO: 29 (miRBase Accession No. MIMAT0013802) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Li H et al., 2009, J Clin Invest., vol. 119, 3666-3677. Furthermore, "hsa-miR-2861" is known to have a precursor, "hsa-mir-2861" (miRBase Accession No. MI0013006, SEQ ID NO: 271), which has a hairpin-like structure.
[0089] As used herein, the term "hsa-miR-296-3p gene" or "hsa-miR-296-3p" encompasses the hsa-miR-296-3p gene set forth in SEQ ID NO: 30 (miRBase Accession No. MIMAT0004679) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Houbaviy HB et al., 2003, Dev Cell., 5, 351-358. Furthermore, the precursor of "hsa-miR-296-3p" is known to be "hsa-mir-296" (miRBase Accession No. MI0000747, SEQ ID NO: 272), which has a hairpin-like structure.
[0090] As used herein, the term "hsa-miR-29b-3p gene" or "hsa-miR-29b-3p" encompasses the hsa-miR-29b-3p gene set forth in SEQ ID NO: 31 (miRBase Accession No. MIMAT0000100) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev., vol. 16, pp. 720-728. Furthermore, known precursors of "hsa-miR-29b-3p" are "hsa-mir-29b-1" (miRBase Accession No. MI0000105, SEQ ID NO: 473) and "hsa-mir-29b-2" (miRBase Accession No. MI0000107, SEQ ID NO: 485), which have a hairpin-like structure.
[0091] As used herein, the term "hsa-miR-3131 gene" or "hsa-miR-3131" encompasses the hsa-miR-3131 gene set forth in SEQ ID NO: 32 (miRBase Accession No. MIMAT0014996) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. It is also known that "hsa-miR-3131" has a precursor, "hsa-mir-3131" (miRBase Accession No. MI0014151, SEQ ID NO: 273), which has a hairpin-like structure.
[0092] As used herein, the term "hsa-miR-3154 gene" or "hsa-miR-3154" encompasses the hsa-miR-3154 gene set forth in SEQ ID NO: 33 (miRBase Accession No. MIMAT0015028) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., 16, 1289-1298. Furthermore, a known precursor of "hsa-miR-3154" is "hsa-mir-3154" (miRBase Accession No. MI0014182, SEQ ID NO: 274), which has a hairpin-like structure.
[0093] As used herein, the term "hsa-miR-3158-5p gene" or "hsa-miR-3158-5p" encompasses the hsa-miR-3158-5p gene set forth in SEQ ID NO: 34 (miRBase Accession No. MIMAT0019211) and homologs or orthologs from other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One., vol. 5, e9637. Furthermore, "hsa-miR-3158-5p" is known to have precursors with hairpin-like structures, namely "hsa-mir-3158-1" (miRBase Accession No. MI0014186, SEQ ID NO: 474) and "hsa-mir-3158-2" (miRBase Accession No. MI0014187, SEQ ID NO: 486).
[0094] As used herein, the term "hsa-miR-3160-5p gene" or "hsa-miR-3160-5p" encompasses the hsa-miR-3160-5p gene set forth in SEQ ID NO: 35 (miRBase Accession No. MIMAT0019212) and homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One, vol. 5, e9685. Furthermore, "hsa-miR-3160-5p" is known to have precursors with hairpin-like structures, "hsa-mir-3160-1" (miRBase Accession No. MI0014189, SEQ ID NO: 475) and "hsa-mir-3160-2" (miRBase Accession No. MI0014190, SEQ ID NO: 487).
[0095] As used herein, the terms "hsa-miR-3162-5p gene" or "hsa-miR-3162-5p" encompass the hsa-miR-3162-5p gene set forth in SEQ ID NO: 36 (miRBase Accession No. MIMAT0015036) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. It is also known that the precursor of "hsa-miR-3162-5p" is "hsa-mir-3162" (miRBase Accession No. MI0014192, SEQ ID NO: 275), which has a hairpin-like structure.
[0096] As used herein, the term "hsa-miR-3178 gene" or "hsa-miR-3178" encompasses the hsa-miR-3178 gene set forth in SEQ ID NO: 37 (miRBase Accession No. MIMAT0015055) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, "hsa-miR-3178" is known to have a precursor, "hsa-mir-3178" (miRBase Accession No. MI0014212, SEQ ID NO: 276), which has a hairpin-like structure.
[0097] As used herein, the term "hsa-miR-3180-3p gene" or "hsa-miR-3180-3p" encompasses the hsa-miR-3180-3p gene set forth in SEQ ID NO: 38 (miRBase Accession No. MIMAT0015058) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One., Vol. 5, e9637. In addition, "hsa-mir-3180-3p" has three known precursors, "hsa-mir-3180-1" (miRBase Accession No. MI0014214, sequence number 496), "hsa-mir-3180-2" (miRBase Accession No. MI0014215, sequence number 497), and "hsa-mir-3180-3" (miRBase Accession No. MI0014217, sequence number 498), which have hairpin-like structures.
[0098] As used herein, the terms "hsa-miR-3184-5p gene" or "hsa-miR-3184-5p" encompass the hsa-miR-3184-5p gene set forth in SEQ ID NO: 39 (miRBase Accession No. MIMAT0015064) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, "hsa-miR-3184-5p" is known to have a precursor, "hsa-mir-3184" (miRBase Accession No. MI0014226, SEQ ID NO: 277), which has a hairpin-like structure.
[0099] As used herein, the term "hsa-miR-3185 gene" or "hsa-miR-3185" encompasses the hsa-miR-3185 gene set forth in SEQ ID NO: 40 (miRBase Accession No. MIMAT0015065) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, "hsa-miR-3185" is known to have a precursor, "hsa-mir-3185" (miRBase Accession No. MI0014227, SEQ ID NO: 278), which has a hairpin-like structure.
[0100] As used herein, the terms "hsa-miR-3194-3p gene" or "hsa-miR-3194-3p" encompass the hsa-miR-3194-3p gene set forth in SEQ ID NO: 41 (miRBase Accession No. MIMAT0019218) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, "hsa-miR-3194-3p" is known to have a precursor, "hsa-mir-3194" (miRBase Accession No. MI0014239, SEQ ID NO: 279), which has a hairpin-like structure.
[0101] As used herein, the term "hsa-miR-3195 gene" or "hsa-miR-3195" encompasses the hsa-miR-3195 gene set forth in SEQ ID NO: 42 (miRBase Accession No. MIMAT0015079) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. Furthermore, "hsa-miR-3195" is known to have a precursor, "hsa-mir-3195" (miRBase Accession No. MI0014240, SEQ ID NO: 280), which has a hairpin-like structure.
[0102] As used herein, the term "hsa-miR-3197 gene" or "hsa-miR-3197" encompasses the hsa-miR-3197 gene set forth in SEQ ID NO: 43 (miRBase Accession No. MIMAT0015082) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Stark MS et al., 2010, PLoS One., vol. 5, e9685. It is also known that "hsa-miR-3197" has a precursor, "hsa-mir-3197" (miRBase Accession No. MI0014245, SEQ ID NO: 281), which has a hairpin-like structure.
[0103] As used herein, the term "hsa-miR-320a gene" or "hsa-miR-320a" encompasses the hsa-miR-320a gene set forth in SEQ ID NO: 44 (miRBase Accession No. MIMAT0000510) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Michael MZ et al., 2003, Mol Cancer Res., vol. 1, pp. 882-891. Furthermore, "hsa-miR-320a" is known to have a precursor, "hsa-mir-320a" (miRBase Accession No. MI0000542, SEQ ID NO: 282), which has a hairpin-like structure.
[0104] As used herein, the term "hsa-miR-320b gene" or "hsa-miR-320b" encompasses the hsa-miR-320b gene set forth in SEQ ID NO: 45 (miRBase Accession No. MIMAT0005792) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., vol. 16, pp. 1289-1298. Furthermore, "hsa-miR-320b" is known to have precursors with hairpin-like structures, such as "hsa-mir-320b-1" (miRBase Accession No. MI0003776, SEQ ID NO: 476) and "hsa-mir-320b-2" (miRBase Accession No. MI0003839, SEQ ID NO: 488).
[0105] As used herein, the terms "hsa-miR-328-5p gene" or "hsa-miR-328-5p" encompass the hsa-miR-328-5p gene set forth in SEQ ID NO: 46 (miRBase Accession No. MIMAT0026486) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Kim J et al., 2004, Proc Natl Acad Sci U S A., vol. 101, 360-365. Furthermore, "hsa-miR-328-5p" is known to have a precursor, "hsa-mir-328" (miRBase Accession No. MI0000804, SEQ ID NO: 283), which has a hairpin-like structure.
[0106] As used herein, the terms "hsa-miR-342-5p gene" or "hsa-miR-342-5p" encompass the hsa-miR-342-5p gene set forth in SEQ ID NO: 47 (miRBase Accession No. MIMAT0004694) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Kim J et al., 2004, Proc Natl Acad Sci U S A., vol. 101, 360-365. Furthermore, the precursor of "hsa-miR-342-5p" is known to be "hsa-mir-342" (miRBase Accession No. MI0000805, SEQ ID NO: 284), which has a hairpin-like structure.
[0107] As used herein, the terms "hsa-miR-345-3p gene" or "hsa-miR-345-3p" encompass the hsa-miR-345-3p gene set forth in SEQ ID NO: 48 (miRBase Accession No. MIMAT0022698) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Kim J et al., 2004, Proc Natl Acad Sci U S A., vol. 101, 360-365. Furthermore, the precursor of "hsa-miR-345-3p" is known to be "hsa-mir-345" (miRBase Accession No. MI0000825, SEQ ID NO: 285), which has a hairpin-like structure.
[0108] As used herein, the terms "hsa-miR-3616-3p gene" or "hsa-miR-3616-3p" encompass the hsa-miR-3616-3p gene set forth in SEQ ID NO: 49 (miRBase Accession No. MIMAT0017996) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. It is also known that the precursor of "hsa-miR-3616-3p" is "hsa-mir-3616" (miRBase Accession No. MI0016006, SEQ ID NO: 286), which has a hairpin-like structure.
[0109] As used herein, the terms "hsa-miR-3619-3p gene" or "hsa-miR-3619-3p" encompass the hsa-miR-3619-3p gene set forth in SEQ ID NO: 50 (miRBase Accession No. MIMAT0019219) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. It is also known that the precursor of "hsa-miR-3619-3p" is "hsa-mir-3619" (miRBase Accession No. MI0016009, SEQ ID NO: 287), which has a hairpin-like structure.
[0110] As used herein, the terms "hsa-miR-3620-5p gene" or "hsa-miR-3620-5p" encompass the hsa-miR-3620-5p gene set forth in SEQ ID NO: 51 (miRBase Accession No. MIMAT0022967) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. It is also known that the precursor of "hsa-miR-3620-5p" is "hsa-mir-3620" (miRBase Accession No. MI0016011, SEQ ID NO: 288), which has a hairpin-like structure.
[0111] As used herein, the term "hsa-miR-3621 gene" or "hsa-miR-3621" encompasses the hsa-miR-3621 gene set forth in SEQ ID NO: 52 (miRBase Accession No. MIMAT0018002) and homologs or orthologs from other species. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. Furthermore, "hsa-miR-3621" is known to have a precursor, "hsa-mir-3621" (miRBase Accession No. MI0016012, SEQ ID NO: 289), which has a hairpin-like structure.
[0112] As used herein, the term "hsa-miR-3622a-5p gene" or "hsa-miR-3622a-5p" encompasses the hsa-miR-3622a-5p gene set forth in SEQ ID NO: 53 (miRBase Accession No. MIMAT0018003) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. Furthermore, the precursor of "hsa-miR-3622a-5p" is known to be "hsa-mir-3622a" (miRBase Accession No. MI0016013, SEQ ID NO: 290), which has a hairpin-like structure.
[0113] As used herein, the term "hsa-miR-3648 gene" or "hsa-miR-3648" encompasses the hsa-miR-3648 gene set forth in SEQ ID NO: 54 (miRBase Accession No. MIMAT0018068) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res., 38, 6234-6246. Furthermore, known precursors of "hsa-miR-3648" include "hsa-mir-3648-1" (miRBase Accession No. MI0016048, SEQ ID NO: 477) and "hsa-mir-3648-2" (miRBase Accession No. MI0031512, SEQ ID NO: 489), which have a hairpin-like structure.
[0114] As used herein, the term "hsa-miR-3652 gene" or "hsa-miR-3652" encompasses the hsa-miR-3652 gene set forth in SEQ ID NO: 55 (miRBase Accession No. MIMAT0018072) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res., 38, 6234-6246. Furthermore, "hsa-miR-3652" is known to have a precursor, "hsa-mir-3652" (miRBase Accession No. MI0016052, SEQ ID NO: 291), which has a hairpin-like structure.
[0115] As used herein, the term "hsa-miR-3656 gene" or "hsa-miR-3656" encompasses the hsa-miR-3656 gene set forth in SEQ ID NO: 56 (miRBase Accession No. MIMAT0018076) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Meiri E et al., 2010, Nucleic Acids Res., 38, 6234-6246. Furthermore, a known precursor of "hsa-miR-3656" is "hsa-mir-3656" (miRBase Accession No. MI0016056, SEQ ID NO: 292), which has a hairpin-like structure.
[0116] As used herein, the terms "hsa-miR-3663-3p gene" or "hsa-miR-3663-3p" encompass the hsa-miR-3663-3p gene set forth in SEQ ID NO: 57 (miRBase Accession No. MIMAT0018085) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Liao JY et al., 2010, PLoS One., Vol. 5, e10563. It is also known that the precursor of "hsa-miR-3663-3p" is "hsa-mir-3663" (miRBase Accession No. MI0016064, SEQ ID NO: 293), which has a hairpin-like structure.
[0117] As used herein, the term "hsa-miR-3679-5p gene" or "hsa-miR-3679-5p" encompasses the hsa-miR-3679-5p gene set forth in SEQ ID NO: 58 (miRBase Accession No. MIMAT0018104) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One., vol. 5, e9637. It is also known that the precursor of "hsa-miR-3679-5p" is "hsa-mir-3679" (miRBase Accession No. MI0016080, SEQ ID NO: 294), which has a hairpin-like structure.
[0118] As used herein, the term "hsa-miR-371b-5p gene" or "hsa-miR-371b-5p" encompasses the hsa-miR-371b-5p gene set forth in SEQ ID NO: 59 (miRBase Accession No. MIMAT0019892) and homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-371b-5p" is known to be "hsa-mir-371b" (miRBase Accession No. MI0017393, SEQ ID NO: 295), which has a hairpin-like structure.
[0119] As used herein, the term "hsa-miR-373-5p gene" or "hsa-miR-373-5p" encompasses the hsa-miR-373-5p gene set forth in SEQ ID NO: 60 (miRBase Accession No. MIMAT0000725) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Suh MR et al., 2004, Dev Biol., vol. 270, pp. 488-498. Furthermore, the precursor of "hsa-miR-373-5p" is known to be "hsa-mir-373" (miRBase Accession No. MI0000781, SEQ ID NO: 296), which has a hairpin-like structure.
[0120] As used herein, the term "hsa-miR-3917 gene" or "hsa-miR-3917" encompasses the hsa-miR-3917 gene set forth in SEQ ID NO: 61 (miRBase Accession No. MIMAT0018191) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Creighton CJ et al., 2010, PLoS One., vol. 5, e9637. Furthermore, "hsa-miR-3917" is known to have a precursor, "hsa-mir-3917" (miRBase Accession No. MI0016423, SEQ ID NO: 297), which has a hairpin-like structure.
[0121] As used herein, the terms "hsa-miR-3940-5p gene" or "hsa-miR-3940-5p" encompass the hsa-miR-3940-5p gene set forth in SEQ ID NO: 62 (miRBase Accession No. MIMAT0019229) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Liao JY et al., 2010, PLoS One., Vol. 5, e10563. Furthermore, "hsa-miR-3940-5p" is known to have a precursor, "hsa-mir-3940" (miRBase Accession No. MI0016597, SEQ ID NO: 298), which has a hairpin-like structure.
[0122] As used herein, the term "hsa-miR-3960 gene" or "hsa-miR-3960" encompasses the hsa-miR-3960 gene set forth in SEQ ID NO: 63 (miRBase Accession No. MIMAT0019337) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Hu R et al., 2011, J Biol Chem., vol. 286, pp. 12328-12339. Furthermore, "hsa-miR-3960" is known to have a precursor, "hsa-mir-3960" (miRBase Accession No. MI0016964, SEQ ID NO: 299), which has a hairpin-like structure.
[0123] As used herein, the term "hsa-miR-4258 gene" or "hsa-miR-4258" encompasses the hsa-miR-4258 gene set forth in SEQ ID NO: 64 (miRBase Accession No. MIMAT0016879) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4258" is known to have a precursor, "hsa-mir-4258" (miRBase Accession No. MI0015857, SEQ ID NO: 300), which has a hairpin-like structure.
[0124] As used herein, the term "hsa-miR-4259 gene" or "hsa-miR-4259" encompasses the hsa-miR-4259 gene set forth in SEQ ID NO: 65 (miRBase Accession No. MIMAT0016880) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4259" is known to have a precursor, "hsa-mir-4259" (miRBase Accession No. MI0015858, SEQ ID NO: 301), which has a hairpin-like structure.
[0125] As used herein, the term "hsa-miR-4270 gene" or "hsa-miR-4270" encompasses the hsa-miR-4270 gene set forth in SEQ ID NO: 66 (miRBase Accession No. MIMAT0016900) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4270" is known to have a precursor, "hsa-mir-4270" (miRBase Accession No. MI0015878, SEQ ID NO: 302), which has a hairpin-like structure.
[0126] As used herein, the term "hsa-miR-4286 gene" or "hsa-miR-4286" encompasses the hsa-miR-4286 gene set forth in SEQ ID NO: 67 (miRBase Accession No. MIMAT0016916) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4286" is known to have a precursor, "hsa-mir-4286" (miRBase Accession No. MI0015894, SEQ ID NO: 303), which has a hairpin-like structure.
[0127] As used herein, the term "hsa-miR-4298 gene" or "hsa-miR-4298" encompasses the hsa-miR-4298 gene set forth in SEQ ID NO: 68 (miRBase Accession No. MIMAT0016852) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4298" is known to have a precursor, "hsa-mir-4298" (miRBase Accession No. MI0015830, SEQ ID NO: 304), which has a hairpin-like structure.
[0128] As used herein, the term "hsa-miR-4322 gene" or "hsa-miR-4322" encompasses the hsa-miR-4322 gene set forth in SEQ ID NO: 69 (miRBase Accession No. MIMAT0016873) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4322" is known to have a precursor, "hsa-mir-4322" (miRBase Accession No. MI0015851, SEQ ID NO: 305), which has a hairpin-like structure.
[0129] As used herein, the term "hsa-miR-4327 gene" or "hsa-miR-4327" encompasses the hsa-miR-4327 gene set forth in SEQ ID NO: 70 (miRBase Accession No. MIMAT0016889) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Goff LA et al., 2009, PLoS One., vol. 4, e7192. Furthermore, "hsa-miR-4327" is known to have a precursor, "hsa-mir-4327" (miRBase Accession No. MI0015867, SEQ ID NO: 306), which has a hairpin-like structure.
[0130] As used herein, the term "hsa-miR-4417 gene" or "hsa-miR-4417" encompasses the hsa-miR-4417 gene set forth in SEQ ID NO: 71 (miRBase Accession No. MIMAT0018929) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4417" is known to have a precursor, "hsa-mir-4417" (miRBase Accession No. MI0016753, SEQ ID NO: 307), which has a hairpin-like structure.
[0131] As used herein, the term "hsa-miR-4419b gene" or "hsa-miR-4419b" encompasses the hsa-miR-4419b gene set forth in SEQ ID NO: 72 (miRBase Accession No. MIMAT0019034) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4419b" is known to have a precursor, "hsa-mir-4419b" (miRBase Accession No. MI0016861, SEQ ID NO: 308), which has a hairpin-like structure.
[0132] As used herein, the term "hsa-miR-4429 gene" or "hsa-miR-4429" encompasses the hsa-miR-4429 gene set forth in SEQ ID NO: 73 (miRBase Accession No. MIMAT0018944) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4429" is known to have a precursor, "hsa-mir-4429" (miRBase Accession No. MI0016768, SEQ ID NO: 309), which has a hairpin-like structure.
[0133] As used herein, the term "hsa-miR-4430 gene" or "hsa-miR-4430" encompasses the hsa-miR-4430 gene set forth in SEQ ID NO: 74 (miRBase Accession No. MIMAT0018945) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4430" is "hsa-mir-4430" (miRBase Accession No. MI0016769, SEQ ID NO: 310), which has a hairpin-like structure.
[0134] As used herein, the terms "hsa-miR-4433a-3p gene" or "hsa-miR-4433a-3p" encompass the hsa-miR-4433a-3p gene set forth in SEQ ID NO: 75 (miRBase Accession No. MIMAT0018949) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, the precursor of "hsa-miR-4433a-3p" is known to be "hsa-mir-4433a" (miRBase Accession No. MI0016773, SEQ ID NO: 311), which has a hairpin-like structure.
[0135] As used herein, the term "hsa-miR-4436b-5p gene" or "hsa-miR-4436b-5p" encompasses the hsa-miR-4436b-5p gene set forth in SEQ ID NO: 76 (miRBase Accession No. MIMAT0019940) and homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., vol. 71, pp. 78-86. Furthermore, "hsa-miR-4436b-5p" is known to have precursors with hairpin-like structures, "hsa-mir-4436b-1" (miRBase Accession No. MI0017425, SEQ ID NO: 478) and "hsa-mir-4436b-2" (miRBase Accession No. MI0019110, SEQ ID NO: 490).
[0136] As used herein, the term "hsa-miR-4443 gene" or "hsa-miR-4443" encompasses the hsa-miR-4443 gene set forth in SEQ ID NO: 77 (miRBase Accession No. MIMAT0018961) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4443" is known to have a precursor, "hsa-mir-4443" (miRBase Accession No. MI0016786, SEQ ID NO: 312), which has a hairpin-like structure.
[0137] As used herein, the terms "hsa-miR-4446-3p gene" or "hsa-miR-4446-3p" encompass the hsa-miR-4446-3p gene set forth in SEQ ID NO: 78 (miRBase Accession No. MIMAT0018965) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, the precursor of "hsa-miR-4446-3p" is known to be "hsa-mir-4446" (miRBase Accession No. MI0016789, SEQ ID NO: 313), which has a hairpin-like structure.
[0138] As used herein, the term "hsa-miR-4447 gene" or "hsa-miR-4447" encompasses the hsa-miR-4447 gene set forth in SEQ ID NO: 79 (miRBase Accession No. MIMAT0018966) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4447" is "hsa-mir-4447" (miRBase Accession No. MI0016790, SEQ ID NO: 314), which has a hairpin-like structure.
[0139] As used herein, the term "hsa-miR-4448 gene" or "hsa-miR-4448" encompasses the hsa-miR-4448 gene set forth in SEQ ID NO: 80 (miRBase Accession No. MIMAT0018967) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4448" is known to have a precursor, "hsa-mir-4448" (miRBase Accession No. MI0016791, SEQ ID NO: 315), which has a hairpin-like structure.
[0140] As used herein, the term "hsa-miR-4449 gene" or "hsa-miR-4449" encompasses the hsa-miR-4449 gene set forth in SEQ ID NO: 81 (miRBase Accession No. MIMAT0018968) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4449" is known to have a precursor, "hsa-mir-4449" (miRBase Accession No. MI0016792, SEQ ID NO: 316), which has a hairpin-like structure.
[0141] As used herein, the term "hsa-miR-4454 gene" or "hsa-miR-4454" encompasses the hsa-miR-4454 gene set forth in SEQ ID NO: 82 (miRBase Accession No. MIMAT0018976) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4454" is "hsa-mir-4454" (miRBase Accession No. MI0016800, SEQ ID NO: 317), which has a hairpin-like structure.
[0142] As used herein, the term "hsa-miR-4455 gene" or "hsa-miR-4455" encompasses the hsa-miR-4455 gene set forth in SEQ ID NO: 83 (miRBase Accession No. MIMAT0018977) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4455" is "hsa-mir-4455" (miRBase Accession No. MI0016801, SEQ ID NO: 318), which has a hairpin-like structure.
[0143] As used herein, the term "hsa-miR-4459 gene" or "hsa-miR-4459" encompasses the hsa-miR-4459 gene set forth in SEQ ID NO: 84 (miRBase Accession No. MIMAT0018981) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4459" is "hsa-mir-4459" (miRBase Accession No. MI0016805, SEQ ID NO: 319), which has a hairpin-like structure.
[0144] As used herein, the term "hsa-miR-4462 gene" or "hsa-miR-4462" encompasses the hsa-miR-4462 gene set forth in SEQ ID NO: 85 (miRBase Accession No. MIMAT0018986) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4462" is known to have a precursor, "hsa-mir-4462" (miRBase Accession No. MI0016810, SEQ ID NO: 320), which has a hairpin-like structure.
[0145] As used herein, the term "hsa-miR-4466 gene" or "hsa-miR-4466" encompasses the hsa-miR-4466 gene set forth in SEQ ID NO: 86 (miRBase Accession No. MIMAT0018993) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4466" is known to have a precursor, "hsa-mir-4466" (miRBase Accession No. MI0016817, SEQ ID NO: 321), which has a hairpin-like structure.
[0146] As used herein, the term "hsa-miR-4467 gene" or "hsa-miR-4467" encompasses the hsa-miR-4467 gene set forth in SEQ ID NO: 87 (miRBase Accession No. MIMAT0018994) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4467" is "hsa-mir-4467" (miRBase Accession No. MI0016818, SEQ ID NO: 322), which has a hairpin-like structure.
[0147] As used herein, the term "hsa-miR-4480 gene" or "hsa-miR-4480" encompasses the hsa-miR-4480 gene set forth in SEQ ID NO: 88 (miRBase Accession No. MIMAT0019014) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4480" is "hsa-mir-4480" (miRBase Accession No. MI0016841, SEQ ID NO: 323), which has a hairpin-like structure.
[0148] As used herein, the term "hsa-miR-4483 gene" or "hsa-miR-4483" encompasses the hsa-miR-4483 gene set forth in SEQ ID NO: 89 (miRBase Accession No. MIMAT0019017) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4483" is "hsa-mir-4483" (miRBase Accession No. MI0016844, SEQ ID NO: 324), which has a hairpin-like structure.
[0149] As used herein, the term "hsa-miR-4484 gene" or "hsa-miR-4484" encompasses the hsa-miR-4484 gene set forth in SEQ ID NO: 90 (miRBase Accession No. MIMAT0019018) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4484" is "hsa-mir-4484" (miRBase Accession No. MI0016845, SEQ ID NO: 325), which has a hairpin-like structure.
[0150] As used herein, the terms "hsa-miR-4485-5p gene" or "hsa-miR-4485-5p" encompass the hsa-miR-4485-5p gene set forth in SEQ ID NO: 91 (miRBase Accession No. MIMAT0032116) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, the precursor of "hsa-miR-4485-5p" is known to be "hsa-mir-4485" (miRBase Accession No. MI0016846, SEQ ID NO: 326), which has a hairpin-like structure.
[0151] As used herein, the term "hsa-miR-4488 gene" or "hsa-miR-4488" encompasses the hsa-miR-4488 gene set forth in SEQ ID NO: 92 (miRBase Accession No. MIMAT0019022) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4488" is known to have a precursor, "hsa-mir-4488" (miRBase Accession No. MI0016849, SEQ ID NO: 327), which has a hairpin-like structure.
[0152] As used herein, the term "hsa-miR-4492 gene" or "hsa-miR-4492" encompasses the hsa-miR-4492 gene set forth in SEQ ID NO: 93 (miRBase Accession No. MIMAT0019027) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4492" is known to have a precursor, "hsa-mir-4492" (miRBase Accession No. MI0016854, SEQ ID NO: 328), which has a hairpin-like structure.
[0153] As used herein, the term "hsa-miR-4505 gene" or "hsa-miR-4505" encompasses the hsa-miR-4505 gene set forth in SEQ ID NO: 94 (miRBase Accession No. MIMAT0019041) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4505" is known to have a precursor, "hsa-mir-4505" (miRBase Accession No. MI0016868, SEQ ID NO: 329), which has a hairpin-like structure.
[0154] As used herein, the term "hsa-miR-4515 gene" or "hsa-miR-4515" encompasses the hsa-miR-4515 gene set forth in SEQ ID NO: 95 (miRBase Accession No. MIMAT0019052) as well as homologs or orthologs from other biological species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, "hsa-miR-4515" is known to have a precursor, "hsa-mir-4515" (miRBase Accession No. MI0016881, SEQ ID NO: 330), which has a hairpin-like structure.
[0155] As used herein, the term "hsa-miR-4525 gene" or "hsa-miR-4525" encompasses the hsa-miR-4525 gene set forth in SEQ ID NO: 96 (miRBase Accession No. MIMAT0019064) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4525" is "hsa-mir-4525" (miRBase Accession No. MI0016892, SEQ ID NO: 331), which has a hairpin-like structure.
[0156] As used herein, the term "hsa-miR-4534 gene" or "hsa-miR-4534" encompasses the hsa-miR-4534 gene set forth in SEQ ID NO: 97 (miRBase Accession No. MIMAT0019073) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4534" is "hsa-mir-4534" (miRBase Accession No. MI0016901, SEQ ID NO: 332), which has a hairpin-like structure.
[0157] As used herein, the term "hsa-miR-4535 gene" or "hsa-miR-4535" encompasses the hsa-miR-4535 gene set forth in SEQ ID NO: 98 (miRBase Accession No. MIMAT0019075) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Jima DD et al., 2010, Blood., vol. 116, e118-e127. Furthermore, a known precursor of "hsa-miR-4535" is "hsa-mir-4535" (miRBase Accession No. MI0016903, SEQ ID NO: 333), which has a hairpin-like structure.
[0158] As used herein, the terms "hsa-miR-4633-3p gene" or "hsa-miR-4633-3p" encompass the hsa-miR-4633-3p gene set forth in SEQ ID NO: 99 (miRBase Accession No. MIMAT0019690) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4633-3p" is known to be "hsa-mir-4633" (miRBase Accession No. MI0017260, SEQ ID NO: 334), which has a hairpin-like structure.
[0159] As used herein, the term "hsa-miR-4634 gene" or "hsa-miR-4634" encompasses the hsa-miR-4634 gene set forth in SEQ ID NO: 100 (miRBase Accession No. MIMAT0019691) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4634" is "hsa-mir-4634" (miRBase Accession No. MI0017261, SEQ ID NO: 335), which has a hairpin-like structure.
[0160] As used herein, the terms "hsa-miR-4640-5p gene" or "hsa-miR-4640-5p" encompass the hsa-miR-4640-5p gene set forth in SEQ ID NO: 101 (miRBase Accession No. MIMAT0019699) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4640-5p" is known to be "hsa-mir-4640" (miRBase Accession No. MI0017267, SEQ ID NO: 336), which has a hairpin-like structure.
[0161] As used herein, the terms "hsa-miR-4649-5p gene" or "hsa-miR-4649-5p" encompass the hsa-miR-4649-5p gene set forth in SEQ ID NO: 102 (miRBase Accession No. MIMAT0019711) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4649-5p" is known to be "hsa-mir-4649" (miRBase Accession No. MI0017276, SEQ ID NO: 337), which has a hairpin-like structure.
[0162] As used herein, the term "hsa-miR-4651 gene" or "hsa-miR-4651" encompasses the hsa-miR-4651 gene set forth in SEQ ID NO: 103 (miRBase Accession No. MIMAT0019715) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4651" is "hsa-mir-4651" (miRBase Accession No. MI0017279, SEQ ID NO: 338), which has a hairpin-like structure.
[0163] As used herein, the terms "hsa-miR-4652-5p gene" or "hsa-miR-4652-5p" encompass the hsa-miR-4652-5p gene set forth in SEQ ID NO: 104 (miRBase Accession No. MIMAT0019716) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4652-5p" is known to be "hsa-mir-4652" (miRBase Accession No. MI0017280, SEQ ID NO: 339), which has a hairpin-like structure.
[0164] As used herein, the terms "hsa-miR-4655-5p gene" or "hsa-miR-4655-5p" encompass the hsa-miR-4655-5p gene set forth in SEQ ID NO: 105 (miRBase Accession No. MIMAT0019721) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4655-5p" is known to have a precursor, "hsa-mir-4655" (miRBase Accession No. MI0017283, SEQ ID NO: 340), which has a hairpin-like structure.
[0165] As used herein, the term "hsa-miR-4656 gene" or "hsa-miR-4656" encompasses the hsa-miR-4656 gene set forth in SEQ ID NO: 106 (miRBase Accession No. MIMAT0019723) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4656" is "hsa-mir-4656" (miRBase Accession No. MI0017284, SEQ ID NO: 341), which has a hairpin-like structure.
[0166] As used herein, the term "hsa-miR-4658 gene" or "hsa-miR-4658" encompasses the hsa-miR-4658 gene set forth in SEQ ID NO: 107 (miRBase Accession No. MIMAT0019725) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4658" is known to have a precursor, "hsa-mir-4658" (miRBase Accession No. MI0017286, SEQ ID NO: 342), which has a hairpin-like structure.
[0167] As used herein, the term "hsa-miR-4663 gene" or "hsa-miR-4663" encompasses the hsa-miR-4663 gene set forth in SEQ ID NO: 108 (miRBase Accession No. MIMAT0019735) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4663" is "hsa-mir-4663" (miRBase Accession No. MI0017292, SEQ ID NO: 343), which has a hairpin-like structure.
[0168] As used herein, the term "hsa-miR-4673 gene" or "hsa-miR-4673" encompasses the hsa-miR-4673 gene set forth in SEQ ID NO: 109 (miRBase Accession No. MIMAT0019755) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4673" is "hsa-mir-4673" (miRBase Accession No. MI0017304, SEQ ID NO: 344), which has a hairpin-like structure.
[0169] As used herein, the term "hsa-miR-4675 gene" or "hsa-miR-4675" encompasses the hsa-miR-4675 gene set forth in SEQ ID NO: 110 (miRBase Accession No. MIMAT0019757) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4675" is "hsa-mir-4675" (miRBase Accession No. MI0017306, SEQ ID NO: 345), which has a hairpin-like structure.
[0170] As used herein, the terms "hsa-miR-4687-3p gene" or "hsa-miR-4687-3p" encompass the hsa-miR-4687-3p gene set forth in SEQ ID NO: 111 (miRBase Accession No. MIMAT0019775) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4687-3p" is known to be "hsa-mir-4687" (miRBase Accession No. MI0017319, SEQ ID NO: 346), which has a hairpin-like structure.
[0171] As used herein, the terms "hsa-miR-4687-5p gene" or "hsa-miR-4687-5p" encompass the hsa-miR-4687-5p gene set forth in SEQ ID NO: 112 (miRBase Accession No. MIMAT0019774) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4687-5p" is known to be "hsa-mir-4687" (miRBase Accession No. MI0017319, SEQ ID NO: 347), which has a hairpin-like structure.
[0172] As used herein, the terms "hsa-miR-4690-5p gene" or "hsa-miR-4690-5p" encompass the hsa-miR-4690-5p gene set forth in SEQ ID NO: 113 (miRBase Accession No. MIMAT0019779) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4690-5p" is known to be "hsa-mir-4690" (miRBase Accession No. MI0017323, SEQ ID NO: 348), which has a hairpin-like structure.
[0173] As used herein, the terms "hsa-miR-4695-5p gene" or "hsa-miR-4695-5p" encompass the hsa-miR-4695-5p gene set forth in SEQ ID NO: 114 (miRBase Accession No. MIMAT0019788) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4695-5p" is known to have a precursor, "hsa-mir-4695" (miRBase Accession No. MI0017328, SEQ ID NO: 349), which has a hairpin-like structure.
[0174] As used herein, the terms "hsa-miR-4697-5p gene" or "hsa-miR-4697-5p" encompass the hsa-miR-4697-5p gene set forth in SEQ ID NO: 115 (miRBase Accession No. MIMAT0019791) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4697-5p" is known to have a precursor, "hsa-mir-4697" (miRBase Accession No. MI0017330, SEQ ID NO: 350), which has a hairpin-like structure.
[0175] As used herein, the term "hsa-miR-4706 gene" or "hsa-miR-4706" encompasses the hsa-miR-4706 gene set forth in SEQ ID NO: 116 (miRBase Accession No. MIMAT0019806) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4706" is "hsa-mir-4706" (miRBase Accession No. MI0017339, SEQ ID NO: 351), which has a hairpin-like structure.
[0176] As used herein, the terms "hsa-miR-4707-3p gene" or "hsa-miR-4707-3p" encompass the hsa-miR-4707-3p gene set forth in SEQ ID NO: 117 (miRBase Accession No. MIMAT0019808) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4707-3p" is known to be "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 352), which has a hairpin-like structure.
[0177] As used herein, the terms "hsa-miR-4707-5p gene" or "hsa-miR-4707-5p" encompass the hsa-miR-4707-5p gene set forth in SEQ ID NO: 118 (miRBase Accession No. MIMAT0019807) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4707-5p" is known to be "hsa-mir-4707" (miRBase Accession No. MI0017340, SEQ ID NO: 353), which has a hairpin-like structure.
[0178] As used herein, the terms "hsa-miR-4708-3p gene" or "hsa-miR-4708-3p" encompass the hsa-miR-4708-3p gene set forth in SEQ ID NO: 119 (miRBase Accession No. MIMAT0019810) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4708-3p" is known to be "hsa-mir-4708" (miRBase Accession No. MI0017341, SEQ ID NO: 354), which has a hairpin-like structure.
[0179] As used herein, the term "hsa-miR-4710 gene" or "hsa-miR-4710" encompasses the hsa-miR-4710 gene set forth in SEQ ID NO: 120 (miRBase Accession No. MIMAT0019815) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4710" is "hsa-mir-4710" (miRBase Accession No. MI0017344, SEQ ID NO: 355), which has a hairpin-like structure.
[0180] As used herein, the term "hsa-miR-4718 gene" or "hsa-miR-4718" encompasses the hsa-miR-4718 gene set forth in SEQ ID NO: 121 (miRBase Accession No. MIMAT0019831) and homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4718" is known to have a precursor, "hsa-mir-4718" (miRBase Accession No. MI0017353, SEQ ID NO: 356), which has a hairpin-like structure.
[0181] As used herein, the terms "hsa-miR-4722-5p gene" or "hsa-miR-4722-5p" encompass the hsa-miR-4722-5p gene set forth in SEQ ID NO: 122 (miRBase Accession No. MIMAT0019836) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4722-5p" is known to be "hsa-mir-4722" (miRBase Accession No. MI0017357, SEQ ID NO: 357), which has a hairpin-like structure.
[0182] As used herein, the terms "hsa-miR-4725-3p gene" or "hsa-miR-4725-3p" encompass the hsa-miR-4725-3p gene set forth in SEQ ID NO: 123 (miRBase Accession No. MIMAT0019844) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4725-3p" is known to be "hsa-mir-4725" (miRBase Accession No. MI0017362, SEQ ID NO: 358), which has a hairpin-like structure.
[0183] As used herein, the terms "hsa-miR-4726-5p gene" or "hsa-miR-4726-5p" encompass the hsa-miR-4726-5p gene set forth in SEQ ID NO: 124 (miRBase Accession No. MIMAT0019845) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4726-5p" is known to be "hsa-mir-4726" (miRBase Accession No. MI0017363, SEQ ID NO: 359), which has a hairpin-like structure.
[0184] As used herein, the terms "hsa-miR-4727-3p gene" or "hsa-miR-4727-3p" encompass the hsa-miR-4727-3p gene set forth in SEQ ID NO: 125 (miRBase Accession No. MIMAT0019848) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4727-3p" is known to be "hsa-mir-4727" (miRBase Accession No. MI0017364, SEQ ID NO: 360), which has a hairpin-like structure.
[0185] As used herein, the terms "hsa-miR-4728-5p gene" or "hsa-miR-4728-5p" encompass the hsa-miR-4728-5p gene set forth in SEQ ID NO: 126 (miRBase Accession No. MIMAT0019849) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4728-5p" is known to have a precursor, "hsa-mir-4728" (miRBase Accession No. MI0017365, SEQ ID NO: 361), which has a hairpin-like structure.
[0186] As used herein, the terms "hsa-miR-4731-5p gene" or "hsa-miR-4731-5p" encompass the hsa-miR-4731-5p gene set forth in SEQ ID NO: 127 (miRBase Accession No. MIMAT0019853) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4731-5p" is known to be "hsa-mir-4731" (miRBase Accession No. MI0017368, SEQ ID NO: 362), which has a hairpin-like structure.
[0187] As used herein, the term "hsa-miR-4736 gene" or "hsa-miR-4736" encompasses the hsa-miR-4736 gene set forth in SEQ ID NO: 128 (miRBase Accession No. MIMAT0019862) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4736" is "hsa-mir-4736" (miRBase Accession No. MI0017373, SEQ ID NO: 363), which has a hairpin-like structure.
[0188] As used herein, the term "hsa-miR-4739 gene" or "hsa-miR-4739" encompasses the hsa-miR-4739 gene set forth in SEQ ID NO: 129 (miRBase Accession No. MIMAT0019868) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4739" is "hsa-mir-4739" (miRBase Accession No. MI0017377, SEQ ID NO: 364), which has a hairpin-like structure.
[0189] As used herein, the terms "hsa-miR-4740-5p gene" or "hsa-miR-4740-5p" encompass the hsa-miR-4740-5p gene set forth in SEQ ID NO: 130 (miRBase Accession No. MIMAT0019869) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4740-5p" is known to be "hsa-mir-4740" (miRBase Accession No. MI0017378, SEQ ID NO: 365), which has a hairpin-like structure.
[0190] As used herein, the term "hsa-miR-4741 gene" or "hsa-miR-4741" encompasses the hsa-miR-4741 gene set forth in SEQ ID NO: 131 (miRBase Accession No. MIMAT0019871) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4741" is "hsa-mir-4741" (miRBase Accession No. MI0017379, SEQ ID NO: 366), which has a hairpin-like structure.
[0191] As used herein, the terms "hsa-miR-4750-5p gene" or "hsa-miR-4750-5p" encompass the hsa-miR-4750-5p gene set forth in SEQ ID NO: 132 (miRBase Accession No. MIMAT0019887) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4750-5p" is known to be "hsa-mir-4750" (miRBase Accession No. MI0017389, SEQ ID NO: 367), which has a hairpin-like structure.
[0192] As used herein, the terms "hsa-miR-4755-3p gene" or "hsa-miR-4755-3p" encompass the hsa-miR-4755-3p gene set forth in SEQ ID NO: 133 (miRBase Accession No. MIMAT0019896) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4755-3p" is known to be "hsa-mir-4755" (miRBase Accession No. MI0017395, SEQ ID NO: 368), which has a hairpin-like structure.
[0193] As used herein, the terms "hsa-miR-4763-3p gene" or "hsa-miR-4763-3p" encompass the hsa-miR-4763-3p gene set forth in SEQ ID NO: 134 (miRBase Accession No. MIMAT0019913) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4763-3p" is known to be "hsa-mir-4763" (miRBase Accession No. MI0017404, SEQ ID NO: 369), which has a hairpin-like structure.
[0194] As used herein, the term "hsa-miR-4771 gene" or "hsa-miR-4771" encompasses the hsa-miR-4771 gene set forth in SEQ ID NO: 135 (miRBase Accession No. MIMAT0019925) and homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, "hsa-miR-4771" is known to have precursors with hairpin-like structures, "hsa-mir-4771-1" (miRBase Accession No. MI0017412, SEQ ID NO: 479) and "hsa-mir-4771-2" (miRBase Accession No. MI0017413, SEQ ID NO: 491).
[0195] As used herein, the terms "hsa-miR-4783-3p gene" or "hsa-miR-4783-3p" encompass the hsa-miR-4783-3p gene set forth in SEQ ID NO: 136 (miRBase Accession No. MIMAT0019947) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4783-3p" is known to be "hsa-mir-4783" (miRBase Accession No. MI0017428, SEQ ID NO: 370), which has a hairpin-like structure.
[0196] As used herein, the terms "hsa-miR-4783-5p gene" or "hsa-miR-4783-5p" encompass the hsa-miR-4783-5p gene set forth in SEQ ID NO: 137 (miRBase Accession No. MIMAT0019946) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4783-5p" is known to be "hsa-mir-4783" (miRBase Accession No. MI0017428, SEQ ID NO: 371), which has a hairpin-like structure.
[0197] As used herein, the terms "hsa-miR-4787-3p gene" or "hsa-miR-4787-3p" encompass the hsa-miR-4787-3p gene set forth in SEQ ID NO: 138 (miRBase Accession No. MIMAT0019957) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, the precursor of "hsa-miR-4787-3p" is known to be "hsa-mir-4787" (miRBase Accession No. MI0017434, SEQ ID NO: 372), which has a hairpin-like structure.
[0198] As used herein, the term "hsa-miR-4792 gene" or "hsa-miR-4792" encompasses the hsa-miR-4792 gene set forth in SEQ ID NO: 139 (miRBase Accession No. MIMAT0019964) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Persson H et al., 2011, Cancer Res., 71, 78-86. Furthermore, a known precursor of "hsa-miR-4792" is "hsa-mir-4792" (miRBase Accession No. MI0017439, SEQ ID NO: 373), which has a hairpin-like structure.
[0199] As used herein, the term "hsa-miR-498 gene" or "hsa-miR-498" encompasses the hsa-miR-498 gene set forth in SEQ ID NO: 140 (miRBase Accession No. MIMAT0002824) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bentwich I et al., 2005, Nat Genet., 37, 766-770. Furthermore, a known precursor of "hsa-miR-498" is "hsa-mir-498" (miRBase Accession No. MI0003142, SEQ ID NO: 374), which has a hairpin-like structure.
[0200] As used herein, the terms "hsa-miR-5008-5p gene" or "hsa-miR-5008-5p" encompass the hsa-miR-5008-5p gene set forth in SEQ ID NO: 141 (miRBase Accession No. MIMAT0021039) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Hansen TB et al., 2011, RNA Biol., 8, 378-383. Furthermore, "hsa-miR-5008-5p" is known to have a precursor, "hsa-mir-5008" (miRBase Accession No. MI0017876, SEQ ID NO: 375), which has a hairpin-like structure.
[0201] As used herein, the terms "hsa-miR-5010-5p gene" or "hsa-miR-5010-5p" encompass the hsa-miR-5010-5p gene set forth in SEQ ID NO: 142 (miRBase Accession No. MIMAT0021043) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Hansen TB et al., 2011, RNA Biol., 8, 378-383. Furthermore, "hsa-miR-5010-5p" is known to have a precursor, "hsa-mir-5010" (miRBase Accession No. MI0017878, SEQ ID NO: 376), which has a hairpin-like structure.
[0202] As used herein, the terms "hsa-miR-504-3p gene" or "hsa-miR-504-3p" encompass the hsa-miR-504-3p gene set forth in SEQ ID NO: 143 (miRBase Accession No. MIMAT0026612) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Bentwich I et al., 2005, Nat Genet., 37, 766-770. Furthermore, the precursor of "hsa-miR-504-3p" is known to be "hsa-mir-504" (miRBase Accession No. MI0003189, SEQ ID NO: 377), which has a hairpin-like structure.
[0203] As used herein, the terms "hsa-miR-5195-3p gene" or "hsa-miR-5195-3p" encompass the hsa-miR-5195-3p gene set forth in SEQ ID NO: 144 (miRBase Accession No. MIMAT0021127) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Schotte D et al., 2011, Leukemia., vol. 25, pp. 1389-1399. Furthermore, the precursor of "hsa-miR-5195-3p" is known to be "hsa-mir-5195" (miRBase Accession No. MI0018174, SEQ ID NO: 378), which has a hairpin-like structure.
[0204] As used herein, the term "hsa-miR-550a-5p gene" or "hsa-miR-550a-5p" encompasses the hsa-miR-550a-5p gene set forth in SEQ ID NO: 145 (miRBase Accession No. MIMAT0004800) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A., vol. 103, pp. 3687-3692. Furthermore, "hsa-miR-550a-5p" is known to have precursors with hairpin-like structures, "hsa-mir-550a-1" (miRBase Accession No. MI0003600, SEQ ID NO: 480) and "hsa-mir-550a-2" (miRBase Accession No. MI0003601, SEQ ID NO: 492).
[0205] As used herein, the term "hsa-miR-5572 gene" or "hsa-miR-5572" encompasses the hsa-miR-5572 gene set forth in SEQ ID NO: 146 (miRBase Accession No. MIMAT0022260) and homologs or orthologs from other species. The gene can be obtained by the method described in Tandon M et al., 2012, Oral Dis., 18:127-131. Furthermore, a known precursor of "hsa-miR-5572" is "hsa-mir-5572" (miRBase Accession No. MI0019117, SEQ ID NO: 379), which has a hairpin-like structure.
[0206] As used herein, the term "hsa-miR-5739 gene" or "hsa-miR-5739" encompasses the hsa-miR-5739 gene set forth in SEQ ID NO: 147 (miRBase Accession No. MIMAT0023116) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Yoo JK et al., 2011, Biochem Biophys Res Commun., vol. 415, pp. 258-262. Furthermore, a known precursor of "hsa-miR-5739" is "hsa-mir-5739" (miRBase Accession No. MI0019412, SEQ ID NO: 380), which has a hairpin-like structure.
[0207] As used herein, the term "hsa-miR-6075 gene" or "hsa-miR-6075" encompasses the hsa-miR-6075 gene set forth in SEQ ID NO: 148 (miRBase Accession No. MIMAT0023700) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Voellenkle C et al., 2012, RNA., 18, 472-484. Furthermore, "hsa-miR-6075" is known to have a precursor, "hsa-mir-6075" (miRBase Accession No. MI0020352, SEQ ID NO: 381), which has a hairpin-like structure.
[0208] As used herein, the term "hsa-miR-6076 gene" or "hsa-miR-6076" encompasses the hsa-miR-6076 gene set forth in SEQ ID NO: 149 (miRBase Accession No. MIMAT0023701) and homologs or orthologs from other species. The gene can be obtained by the method described in Voellenkle C et al., 2012, RNA., 18, 472-484. Furthermore, "hsa-miR-6076" is known to have a precursor, "hsa-mir-6076" (miRBase Accession No. MI0020353, SEQ ID NO: 382), which has a hairpin-like structure.
[0209] As used herein, the term "hsa-miR-6088 gene" or "hsa-miR-6088" encompasses the hsa-miR-6088 gene set forth in SEQ ID NO: 150 (miRBase Accession No. MIMAT0023713) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Yoo JK et al., 2012, Stem Cells Dev., vol. 21, pp. 2049-2057. Furthermore, "hsa-miR-6088" is known to have a precursor, "hsa-mir-6088" (miRBase Accession No. MI0020365, SEQ ID NO: 383), which has a hairpin-like structure.
[0210] As used herein, the term "hsa-miR-6124 gene" or "hsa-miR-6124" encompasses the hsa-miR-6124 gene set forth in SEQ ID NO: 151 (miRBase Accession No. MIMAT0024597) as well as homologs or orthologs from other biological species. The gene can be obtained by the method described in Smith JL et al., 2012, J Virol., vol. 86, pp. 5278-5287. Furthermore, "hsa-miR-6124" is known to have a precursor, "hsa-mir-6124" (miRBase Accession No. MI0021258, SEQ ID NO: 384), which has a hairpin-like structure.
[0211] As used herein, the term "hsa-miR-6131 gene" or "hsa-miR-6131" encompasses the hsa-miR-6131 gene set forth in SEQ ID NO: 152 (miRBase Accession No. MIMAT0024615) and homologs or orthologs from other species. The gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol., vol. 4, pp. 552-564. Furthermore, "hsa-miR-6131" is known to have a precursor, "hsa-mir-6131" (miRBase Accession No. MI0021276, SEQ ID NO: 385), which has a hairpin-like structure.
[0212] As used herein, the term "hsa-miR-6132 gene" or "hsa-miR-6132" encompasses the hsa-miR-6132 gene set forth in SEQ ID NO: 153 (miRBase Accession No. MIMAT0024616) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Dannemann M et al., 2012, Genome Biol Evol., vol. 4, pp. 552-564. Furthermore, a known precursor of "hsa-miR-6132" is "hsa-mir-6132" (miRBase Accession No. MI0021277, SEQ ID NO: 386), which has a hairpin-like structure.
[0213] As used herein, the term "hsa-miR-614 gene" or "hsa-miR-614" encompasses the hsa-miR-614 gene set forth in SEQ ID NO: 154 (miRBase Accession No. MIMAT0003282) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A., vol. 103, 3687-3692. Furthermore, "hsa-miR-614" is known to have a precursor, "hsa-mir-614" (miRBase Accession No. MI0003627, SEQ ID NO: 387), which has a hairpin-like structure.
[0214] As used herein, the terms "hsa-miR-615-5p gene" or "hsa-miR-615-5p" encompass the hsa-miR-615-5p gene set forth in SEQ ID NO: 155 (miRBase Accession No. MIMAT0004804) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A., vol. 103, 3687-3692. Furthermore, "hsa-miR-615-5p" is known to have a precursor, "hsa-mir-615" (miRBase Accession No. MI0003628, SEQ ID NO: 388), which has a hairpin-like structure.
[0215] As used herein, the terms "hsa-miR-619-5p gene" or "hsa-miR-619-5p" encompass the hsa-miR-619-5p gene set forth in SEQ ID NO: 156 (miRBase Accession No. MIMAT0026622) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A., vol. 103, 3687-3692. Furthermore, "hsa-miR-619-5p" is known to have a precursor, "hsa-mir-619" (miRBase Accession No. MI0003633, SEQ ID NO: 389), which has a hairpin-like structure.
[0216] As used herein, the terms "hsa-miR-642b-3p gene" or "hsa-miR-642b-3p" encompass the hsa-miR-642b-3p gene set forth in SEQ ID NO: 157 (miRBase Accession No. MIMAT0018444) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Witten D et al., 2010, BMC Biol., 8, 58. Furthermore, the precursor of "hsa-miR-642b-3p" is known to be "hsa-mir-642b" (miRBase Accession No. MI0016685, SEQ ID NO: 390), which has a hairpin-like structure.
[0217] As used herein, the terms "hsa-miR-6510-5p gene" or "hsa-miR-6510-5p" encompass the hsa-miR-6510-5p gene set forth in SEQ ID NO: 158 (miRBase Accession No. MIMAT0025476) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet., 20, 4025-4040. Furthermore, the precursor of "hsa-miR-6510-5p" is known to be "hsa-mir-6510" (miRBase Accession No. MI0022222, SEQ ID NO: 391), which has a hairpin-like structure.
[0218] As used herein, the term "hsa-miR-6511a-5p gene" or "hsa-miR-6511a-5p" encompasses the hsa-miR-6511a-5p gene set forth in SEQ ID NO: 159 (miRBase Accession No. MIMAT0025478) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet., 20, 4025-4040. Furthermore, "hsa-mir-6511a-5p" has three known precursors, "hsa-mir-6511a-1" (miRBase Accession No. MI0022223, SEQ ID NO: 499), "hsa-mir-6511a-2" (miRBase Accession No. MI0023564, SEQ ID NO: 501), "hsa-mir-6511a-3" (miRBase Accession No. MI0023565, SEQ ID NO: 503), and "hsa-mir-6511a-4" (miRBase Accession No. MI0023566, SEQ ID NO: 505), which have hairpin-like structures.
[0219] As used herein, the terms "hsa-miR-6515-3p gene" or "hsa-miR-6515-3p" encompass the hsa-miR-6515-3p gene set forth in SEQ ID NO: 160 (miRBase Accession No. MIMAT0025487) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet., vol. 20, pp. 4025-4040. Furthermore, the precursor of "hsa-miR-6515-3p" is known to be "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 392), which has a hairpin-like structure.
[0220] As used herein, the terms "hsa-miR-6515-5p gene" or "hsa-miR-6515-5p" encompass the hsa-miR-6515-5p gene set forth in SEQ ID NO: 161 (miRBase Accession No. MIMAT0025486) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Joyce CE et al., 2011, Hum Mol Genet., 20, 4025-4040. Furthermore, "hsa-miR-6515-5p" is known to have a precursor, "hsa-mir-6515" (miRBase Accession No. MI0022227, SEQ ID NO: 393), which has a hairpin-like structure.
[0221] As used herein, the term "hsa-miR-663b gene" or "hsa-miR-663b" encompasses the hsa-miR-663b gene set forth in SEQ ID NO: 162 (miRBase Accession No. MIMAT0005867) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Takada S et al., 2008, Leukemia., 22, 1274-1278. Furthermore, "hsa-miR-663b" is known to have a precursor, "hsa-mir-663b" (miRBase Accession No. MI0006336, SEQ ID NO: 394), which has a hairpin-like structure.
[0222] As used herein, the term "hsa-miR-6716-5p gene" or "hsa-miR-6716-5p" encompasses the hsa-miR-6716-5p gene set forth in SEQ ID NO: 163 (miRBase Accession No. MIMAT0025844) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Li Y et al., 2012, Gene., vol. 497, pp. 330-335. Furthermore, the precursor of "hsa-miR-6716-5p" is known to be "hsa-mir-6716" (miRBase Accession No. MI0022550, SEQ ID NO: 395), which has a hairpin-like structure.
[0223] As used herein, the terms "hsa-miR-6717-5p gene" or "hsa-miR-6717-5p" encompass the hsa-miR-6717-5p gene set forth in SEQ ID NO: 164 (miRBase Accession No. MIMAT0025846) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Li Y et al., 2012, Gene., vol. 497, pp. 330-335. Furthermore, the precursor of "hsa-miR-6717-5p" is known to be "hsa-mir-6717" (miRBase Accession No. MI0022551, SEQ ID NO: 396), which has a hairpin-like structure.
[0224] As used herein, the terms "hsa-miR-6722-3p gene" or "hsa-miR-6722-3p" encompass the hsa-miR-6722-3p gene set forth in SEQ ID NO: 165 (miRBase Accession No. MIMAT0025854) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Li Y et al., 2012, Gene., vol. 497, pp. 330-335. Furthermore, the precursor of "hsa-miR-6722-3p" is known to be "hsa-mir-6722" (miRBase Accession No. MI0022557, SEQ ID NO: 397), which has a hairpin-like structure.
[0225] As used herein, the term "hsa-miR-6724-5p gene" or "hsa-miR-6724-5p" encompasses the hsa-miR-6724-5p gene set forth in SEQ ID NO: 166 (miRBase Accession No. MIMAT0025856) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Li Y et al., 2012, Gene., 497, 330-335. In addition, "hsa-mir-6724-5p" has three known precursors, "hsa-mir-6724-1" (miRBase Accession No. MI0022559, SEQ ID NO: 500), "hsa-mir-6724-2" (miRBase Accession No. MI0031516, SEQ ID NO: 502), "hsa-mir-6724-3" (miRBase Accession No. MI0031517, SEQ ID NO: 504), and "hsa-mir-6724-4" (miRBase Accession No. MI0031518, SEQ ID NO: 506), which have hairpin-like structures.
[0226] As used herein, the term "hsa-miR-6726-5p gene" or "hsa-miR-6726-5p" encompasses the hsa-miR-6726-5p gene set forth in SEQ ID NO: 167 (miRBase Accession No. MIMAT0027353) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6726-5p" is known to have a precursor, "hsa-mir-6726" (miRBase Accession No. MI0022571, SEQ ID NO: 398), which has a hairpin-like structure.
[0227] As used herein, the term "hsa-miR-6737-5p gene" or "hsa-miR-6737-5p" encompasses the hsa-miR-6737-5p gene set forth in SEQ ID NO: 168 (miRBase Accession No. MIMAT0027375) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6737-5p" is known to be "hsa-mir-6737" (miRBase Accession No. MI0022582, SEQ ID NO: 399), which has a hairpin-like structure.
[0228] As used herein, the term "hsa-miR-6741-5p gene" or "hsa-miR-6741-5p" encompasses the hsa-miR-6741-5p gene set forth in SEQ ID NO: 169 (miRBase Accession No. MIMAT0027383) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6741-5p" is known to be "hsa-mir-6741" (miRBase Accession No. MI0022586, SEQ ID NO: 400), which has a hairpin-like structure.
[0229] As used herein, the term "hsa-miR-6742-5p gene" or "hsa-miR-6742-5p" encompasses the hsa-miR-6742-5p gene set forth in SEQ ID NO: 170 (miRBase Accession No. MIMAT0027385) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6742-5p" is known to have a precursor, "hsa-mir-6742" (miRBase Accession No. MI0022587, SEQ ID NO: 401), which has a hairpin-like structure.
[0230] As used herein, the term "hsa-miR-6743-5p gene" or "hsa-miR-6743-5p" encompasses the hsa-miR-6743-5p gene set forth in SEQ ID NO: 171 (miRBase Accession No. MIMAT0027387) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6743-5p" is known to be "hsa-mir-6743" (miRBase Accession No. MI0022588, SEQ ID NO: 402), which has a hairpin-like structure.
[0231] As used herein, the term "hsa-miR-6746-5p gene" or "hsa-miR-6746-5p" encompasses the hsa-miR-6746-5p gene set forth in SEQ ID NO: 172 (miRBase Accession No. MIMAT0027392) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6746-5p" is known to be "hsa-mir-6746" (miRBase Accession No. MI0022591, SEQ ID NO: 403), which has a hairpin-like structure.
[0232] As used herein, the term "hsa-miR-6749-5p gene" or "hsa-miR-6749-5p" encompasses the hsa-miR-6749-5p gene set forth in SEQ ID NO: 173 (miRBase Accession No. MIMAT0027398) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6749-5p" is known to be "hsa-mir-6749" (miRBase Accession No. MI0022594, SEQ ID NO: 404), which has a hairpin-like structure.
[0233] As used herein, the terms "hsa-miR-6760-5p gene" or "hsa-miR-6760-5p" encompass the hsa-miR-6760-5p gene set forth in SEQ ID NO: 174 (miRBase Accession No. MIMAT0027420) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6760-5p" is known to be "hsa-mir-6760" (miRBase Accession No. MI0022605, SEQ ID NO: 405), which has a hairpin-like structure.
[0234] As used herein, the term "hsa-miR-6762-5p gene" or "hsa-miR-6762-5p" encompasses the hsa-miR-6762-5p gene set forth in SEQ ID NO: 175 (miRBase Accession No. MIMAT0027424) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6762-5p" is known to be "hsa-mir-6762" (miRBase Accession No. MI0022607, SEQ ID NO: 406), which has a hairpin-like structure.
[0235] As used herein, the term "hsa-miR-6765-3p gene" or "hsa-miR-6765-3p" encompasses the hsa-miR-6765-3p gene set forth in SEQ ID NO: 176 (miRBase Accession No. MIMAT0027431) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6765-3p" is known to be "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 407), which has a hairpin-like structure.
[0236] As used herein, the term "hsa-miR-6765-5p gene" or "hsa-miR-6765-5p" encompasses the hsa-miR-6765-5p gene set forth in SEQ ID NO: 177 (miRBase Accession No. MIMAT0027430) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6765-5p" is known to be "hsa-mir-6765" (miRBase Accession No. MI0022610, SEQ ID NO: 408), which has a hairpin-like structure.
[0237] As used herein, the term "hsa-miR-6766-3p gene" or "hsa-miR-6766-3p" encompasses the hsa-miR-6766-3p gene set forth in SEQ ID NO: 178 (miRBase Accession No. MIMAT0027433) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6766-3p" is known to be "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 409), which has a hairpin-like structure.
[0238] As used herein, the term "hsa-miR-6766-5p gene" or "hsa-miR-6766-5p" encompasses the hsa-miR-6766-5p gene set forth in SEQ ID NO: 179 (miRBase Accession No. MIMAT0027432) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6766-5p" is known to be "hsa-mir-6766" (miRBase Accession No. MI0022611, SEQ ID NO: 410), which has a hairpin-like structure.
[0239] As used herein, the term "hsa-miR-6771-5p gene" or "hsa-miR-6771-5p" encompasses the hsa-miR-6771-5p gene set forth in SEQ ID NO: 180 (miRBase Accession No. MIMAT0027442) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6771-5p" is known to be "hsa-mir-6771" (miRBase Accession No. MI0022616, SEQ ID NO: 411), which has a hairpin-like structure.
[0240] As used herein, the term "hsa-miR-6774-5p gene" or "hsa-miR-6774-5p" encompasses the hsa-miR-6774-5p gene set forth in SEQ ID NO: 181 (miRBase Accession No. MIMAT0027448) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6774-5p" is known to be "hsa-mir-6774" (miRBase Accession No. MI0022619, SEQ ID NO: 412), which has a hairpin-like structure.
[0241] As used herein, the term "hsa-miR-6777-5p gene" or "hsa-miR-6777-5p" encompasses the hsa-miR-6777-5p gene set forth in SEQ ID NO: 182 (miRBase Accession No. MIMAT0027454) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6777-5p" is known to be "hsa-mir-6777" (miRBase Accession No. MI0022622, SEQ ID NO: 413), which has a hairpin-like structure.
[0242] As used herein, the term "hsa-miR-6778-5p gene" or "hsa-miR-6778-5p" encompasses the hsa-miR-6778-5p gene set forth in SEQ ID NO: 183 (miRBase Accession No. MIMAT0027456) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6778-5p" is known to be "hsa-mir-6778" (miRBase Accession No. MI0022623, SEQ ID NO: 414), which has a hairpin-like structure.
[0243] As used herein, the term "hsa-miR-6780b-5p gene" or "hsa-miR-6780b-5p" encompasses the hsa-miR-6780b-5p gene set forth in SEQ ID NO: 184 (miRBase Accession No. MIMAT0027572) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6780b-5p" is known to be "hsa-mir-6780b" (miRBase Accession No. MI0022681, SEQ ID NO: 415), which has a hairpin-like structure.
[0244] As used herein, the term "hsa-miR-6781-5p gene" or "hsa-miR-6781-5p" encompasses the hsa-miR-6781-5p gene set forth in SEQ ID NO: 185 (miRBase Accession No. MIMAT0027462) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6781-5p" is known to have a precursor, "hsa-mir-6781" (miRBase Accession No. MI0022626, SEQ ID NO: 416), which has a hairpin-like structure.
[0245] As used herein, the term "hsa-miR-6782-5p gene" or "hsa-miR-6782-5p" encompasses the hsa-miR-6782-5p gene set forth in SEQ ID NO: 186 (miRBase Accession No. MIMAT0027464) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6782-5p" is known to be "hsa-mir-6782" (miRBase Accession No. MI0022627, SEQ ID NO: 417), which has a hairpin-like structure.
[0246] As used herein, the term "hsa-miR-6784-5p gene" or "hsa-miR-6784-5p" encompasses the hsa-miR-6784-5p gene set forth in SEQ ID NO: 187 (miRBase Accession No. MIMAT0027468) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6784-5p" is known to be "hsa-mir-6784" (miRBase Accession No. MI0022629, SEQ ID NO: 418), which has a hairpin-like structure.
[0247] As used herein, the term "hsa-miR-6785-5p gene" or "hsa-miR-6785-5p" encompasses the hsa-miR-6785-5p gene set forth in SEQ ID NO: 188 (miRBase Accession No. MIMAT0027470) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6785-5p" is known to have a precursor, "hsa-mir-6785" (miRBase Accession No. MI0022630, SEQ ID NO: 419), which has a hairpin-like structure.
[0248] As used herein, the term "hsa-miR-6787-5p gene" or "hsa-miR-6787-5p" encompasses the hsa-miR-6787-5p gene set forth in SEQ ID NO: 189 (miRBase Accession No. MIMAT0027474) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6787-5p" is known to be "hsa-mir-6787" (miRBase Accession No. MI0022632, SEQ ID NO: 420), which has a hairpin-like structure.
[0249] As used herein, the term "hsa-miR-6789-5p gene" or "hsa-miR-6789-5p" encompasses the hsa-miR-6789-5p gene set forth in SEQ ID NO: 190 (miRBase Accession No. MIMAT0027478) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6789-5p" is known to have a precursor, "hsa-mir-6789" (miRBase Accession No. MI0022634, SEQ ID NO: 421), which has a hairpin-like structure.
[0250] As used herein, the term "hsa-miR-6791-5p gene" or "hsa-miR-6791-5p" encompasses the hsa-miR-6791-5p gene set forth in SEQ ID NO: 191 (miRBase Accession No. MIMAT0027482) and homologs or orthologs from other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6791-5p" is known to be "hsa-mir-6791" (miRBase Accession No. MI0022636, SEQ ID NO: 422), which has a hairpin-like structure.
[0251] As used herein, the term "hsa-miR-6794-5p gene" or "hsa-miR-6794-5p" encompasses the hsa-miR-6794-5p gene set forth in SEQ ID NO: 192 (miRBase Accession No. MIMAT0027488) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6794-5p" is known to be "hsa-mir-6794" (miRBase Accession No. MI0022639, SEQ ID NO: 423), which has a hairpin-like structure.
[0252] As used herein, the term "hsa-miR-6800-5p gene" or "hsa-miR-6800-5p" encompasses the hsa-miR-6800-5p gene set forth in SEQ ID NO: 193 (miRBase Accession No. MIMAT0027500) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6800-5p" is known to have a precursor, "hsa-mir-6800" (miRBase Accession No. MI0022645, SEQ ID NO: 424), which has a hairpin-like structure.
[0253] As used herein, the terms "hsa-miR-6802-5p gene" or "hsa-miR-6802-5p" encompass the hsa-miR-6802-5p gene set forth in SEQ ID NO: 194 (miRBase Accession No. MIMAT0027504) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6802-5p" is known to be "hsa-mir-6802" (miRBase Accession No. MI0022647, SEQ ID NO: 425), which has a hairpin-like structure.
[0254] As used herein, the term "hsa-miR-6803-5p gene" or "hsa-miR-6803-5p" encompasses the hsa-miR-6803-5p gene set forth in SEQ ID NO: 195 (miRBase Accession No. MIMAT0027506) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6803-5p" is known to be "hsa-mir-6803" (miRBase Accession No. MI0022648, SEQ ID NO: 426), which has a hairpin-like structure.
[0255] As used herein, the terms "hsa-miR-6812-5p gene" or "hsa-miR-6812-5p" encompass the hsa-miR-6812-5p gene set forth in SEQ ID NO: 196 (miRBase Accession No. MIMAT0027524) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6812-5p" is known to be "hsa-mir-6812" (miRBase Accession No. MI0022657, SEQ ID NO: 427), which has a hairpin-like structure.
[0256] As used herein, the term "hsa-miR-6816-5p gene" or "hsa-miR-6816-5p" encompasses the hsa-miR-6816-5p gene set forth in SEQ ID NO: 197 (miRBase Accession No. MIMAT0027532) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6816-5p" is known to be "hsa-mir-6816" (miRBase Accession No. MI0022661, SEQ ID NO: 428), which has a hairpin-like structure.
[0257] As used herein, the term "hsa-miR-6819-5p gene" or "hsa-miR-6819-5p" encompasses the hsa-miR-6819-5p gene set forth in SEQ ID NO: 198 (miRBase Accession No. MIMAT0027538) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6819-5p" is known to have a precursor, "hsa-mir-6819" (miRBase Accession No. MI0022664, SEQ ID NO: 429), which has a hairpin-like structure.
[0258] As used herein, the term "hsa-miR-6821-5p gene" or "hsa-miR-6821-5p" encompasses the hsa-miR-6821-5p gene set forth in SEQ ID NO: 199 (miRBase Accession No. MIMAT0027542) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6821-5p" is known to be "hsa-mir-6821" (miRBase Accession No. MI0022666, SEQ ID NO: 430), which has a hairpin-like structure.
[0259] As used herein, the terms "hsa-miR-6826-5p gene" or "hsa-miR-6826-5p" encompass the hsa-miR-6826-5p gene set forth in SEQ ID NO: 200 (miRBase Accession No. MIMAT0027552) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6826-5p" is known to be "hsa-mir-6826" (miRBase Accession No. MI0022671, SEQ ID NO: 431), which has a hairpin-like structure.
[0260] As used herein, the term "hsa-miR-6831-5p gene" or "hsa-miR-6831-5p" encompasses the hsa-miR-6831-5p gene set forth in SEQ ID NO: 201 (miRBase Accession No. MIMAT0027562) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6831-5p" is known to be "hsa-mir-6831" (miRBase Accession No. MI0022676, SEQ ID NO: 432), which has a hairpin-like structure.
[0261] As used herein, the term "hsa-miR-6836-3p gene" or "hsa-miR-6836-3p" encompasses the hsa-miR-6836-3p gene set forth in SEQ ID NO: 202 (miRBase Accession No. MIMAT0027575) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6836-3p" is known to be "hsa-mir-6836" (miRBase Accession No. MI0022682, SEQ ID NO: 433), which has a hairpin-like structure.
[0262] As used herein, the term "hsa-miR-6840-3p gene" or "hsa-miR-6840-3p" encompasses the hsa-miR-6840-3p gene set forth in SEQ ID NO: 203 (miRBase Accession No. MIMAT0027583) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6840-3p" is known to be "hsa-mir-6840" (miRBase Accession No. MI0022686, SEQ ID NO: 434), which has a hairpin-like structure.
[0263] As used herein, the terms "hsa-miR-6842-5p gene" or "hsa-miR-6842-5p" encompass the hsa-miR-6842-5p gene set forth in SEQ ID NO: 204 (miRBase Accession No. MIMAT0027586) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6842-5p" is known to have a precursor, "hsa-mir-6842" (miRBase Accession No. MI0022688, SEQ ID NO: 435), which has a hairpin-like structure.
[0264] As used herein, the terms "hsa-miR-6850-5p gene" or "hsa-miR-6850-5p" encompass the hsa-miR-6850-5p gene set forth in SEQ ID NO: 205 (miRBase Accession No. MIMAT0027600) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6850-5p" is known to have a precursor, "hsa-mir-6850" (miRBase Accession No. MI0022696, SEQ ID NO: 436), which has a hairpin-like structure.
[0265] As used herein, the terms "hsa-miR-6861-5p gene" or "hsa-miR-6861-5p" encompass the hsa-miR-6861-5p gene set forth in SEQ ID NO: 206 (miRBase Accession No. MIMAT0027623) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6861-5p" is known to be "hsa-mir-6861" (miRBase Accession No. MI0022708, SEQ ID NO: 437), which has a hairpin-like structure.
[0266] As used herein, the term "hsa-miR-6869-5p gene" or "hsa-miR-6869-5p" encompasses the hsa-miR-6869-5p gene set forth in SEQ ID NO: 207 (miRBase Accession No. MIMAT0027638) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6869-5p" is known to have a precursor, "hsa-mir-6869" (miRBase Accession No. MI0022716, SEQ ID NO: 438), which has a hairpin-like structure.
[0267] As used herein, the term "hsa-miR-6870-5p gene" or "hsa-miR-6870-5p" encompasses the hsa-miR-6870-5p gene set forth in SEQ ID NO: 208 (miRBase Accession No. MIMAT0027640) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6870-5p" is known to be "hsa-mir-6870" (miRBase Accession No. MI0022717, SEQ ID NO: 439), which has a hairpin-like structure.
[0268] As used herein, the term "hsa-miR-6877-5p gene" or "hsa-miR-6877-5p" encompasses the hsa-miR-6877-5p gene set forth in SEQ ID NO: 209 (miRBase Accession No. MIMAT0027654) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6877-5p" is known to be "hsa-mir-6877" (miRBase Accession No. MI0022724, SEQ ID NO: 440), which has a hairpin-like structure.
[0269] As used herein, the term "hsa-miR-6879-5p gene" or "hsa-miR-6879-5p" encompasses the hsa-miR-6879-5p gene set forth in SEQ ID NO: 210 (miRBase Accession No. MIMAT0027658) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6879-5p" is known to have a precursor, "hsa-mir-6879" (miRBase Accession No. MI0022726, SEQ ID NO: 441), which has a hairpin-like structure.
[0270] As used herein, the terms "hsa-miR-6880-3p gene" or "hsa-miR-6880-3p" encompass the hsa-miR-6880-3p gene set forth in SEQ ID NO: 211 (miRBase Accession No. MIMAT0027661) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-6880-3p" is known to be "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 442), which has a hairpin-like structure.
[0271] As used herein, the terms "hsa-miR-6880-5p gene" or "hsa-miR-6880-5p" encompass the hsa-miR-6880-5p gene set forth in SEQ ID NO: 212 (miRBase Accession No. MIMAT0027660) and homologs or orthologs from other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6880-5p" is known to have a precursor, "hsa-mir-6880" (miRBase Accession No. MI0022727, SEQ ID NO: 443), which has a hairpin-like structure.
[0272] As used herein, the term "hsa-miR-6885-5p gene" or "hsa-miR-6885-5p" encompasses the hsa-miR-6885-5p gene set forth in SEQ ID NO: 213 (miRBase Accession No. MIMAT0027670) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6885-5p" is known to have a precursor, "hsa-mir-6885" (miRBase Accession No. MI0022732, SEQ ID NO: 444), which has a hairpin-like structure.
[0273] As used herein, the terms "hsa-miR-6887-5p gene" or "hsa-miR-6887-5p" encompass the hsa-miR-6887-5p gene set forth in SEQ ID NO: 214 (miRBase Accession No. MIMAT0027674) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-6887-5p" is known to have a precursor, "hsa-mir-6887" (miRBase Accession No. MI0022734, SEQ ID NO: 445), which has a hairpin-like structure.
[0274] As used herein, the terms "hsa-miR-7107-5p gene" or "hsa-miR-7107-5p" encompass the hsa-miR-7107-5p gene set forth in SEQ ID NO: 215 (miRBase Accession No. MIMAT0028111) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7107-5p" is known to be "hsa-mir-7107" (miRBase Accession No. MI0022958, SEQ ID NO: 446), which has a hairpin-like structure.
[0275] As used herein, the terms "hsa-miR-7108-3p gene" or "hsa-miR-7108-3p" encompass the hsa-miR-7108-3p gene set forth in SEQ ID NO: 216 (miRBase Accession No. MIMAT0028114) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, "hsa-miR-7108-3p" is known to have a precursor, "hsa-mir-7108" (miRBase Accession No. MI0022959, SEQ ID NO: 447), which has a hairpin-like structure.
[0276] As used herein, the terms "hsa-miR-7109-5p gene" or "hsa-miR-7109-5p" encompass the hsa-miR-7109-5p gene set forth in SEQ ID NO: 217 (miRBase Accession No. MIMAT0028115) and homologs or orthologs from other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7109-5p" is known to be "hsa-mir-7109" (miRBase Accession No. MI0022960, SEQ ID NO: 448), which has a hairpin-like structure.
[0277] As used herein, the term "hsa-miR-711 gene" or "hsa-miR-711" encompasses the hsa-miR-711 gene set forth in SEQ ID NO: 218 (miRBase Accession No. MIMAT0012734) and homologs or orthologs from other species. The gene can be obtained by the method described in Artzi S et al., 2008, BMC Bioinformatics, 9, 39. Furthermore, "hsa-miR-711" is known to have a precursor, "hsa-mir-711" (miRBase Accession No. MI0012488, SEQ ID NO: 449), which has a hairpin-like structure.
[0278] As used herein, the term "hsa-miR-7113-3p gene" or "hsa-miR-7113-3p" encompasses the hsa-miR-7113-3p gene set forth in SEQ ID NO: 219 (miRBase Accession No. MIMAT0028124) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res., vol. 22, pp. 1634-1645. Furthermore, the precursor of "hsa-miR-7113-3p" is known to be "hsa-mir-7113" (miRBase Accession No. MI0022964, SEQ ID NO: 450), which has a hairpin-like structure.
[0279] As used herein, the term "hsa-miR-7150 gene" or "hsa-miR-7150" encompasses the hsa-miR-7150 gene set forth in SEQ ID NO: 220 (miRBase Accession No. MIMAT0028211) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Oulas A et al., 2009, Nucleic Acids Res., 37, 3276-3287. Furthermore, a known precursor of "hsa-miR-7150" is "hsa-mir-7150" (miRBase Accession No. MI0023610, SEQ ID NO: 451), which has a hairpin-like structure.
[0280] As used herein, the terms "hsa-miR-744-5p gene" or "hsa-miR-744-5p" encompass the hsa-miR-744-5p gene set forth in SEQ ID NO: 221 (miRBase Accession No. MIMAT0004945) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., vol. 16, pp. 1289-1298. Furthermore, the precursor of "hsa-miR-744-5p" is known to be "hsa-mir-744" (miRBase Accession No. MI0005559, SEQ ID NO: 452), which has a hairpin-like structure.
[0281] As used herein, the term "hsa-miR-7975 gene" or "hsa-miR-7975" encompasses the hsa-miR-7975 gene set forth in SEQ ID NO: 222 (miRBase Accession No. MIMAT0031178) and homologs or orthologs from other species. The gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol., vol. 27, pp. 1128-1141. Furthermore, a known precursor of "hsa-miR-7975" is "hsa-mir-7975" (miRBase Accession No. MI0025751, SEQ ID NO: 453), which has a hairpin-like structure.
[0282] As used herein, the term "hsa-miR-7977 gene" or "hsa-miR-7977" encompasses the hsa-miR-7977 gene set forth in SEQ ID NO: 223 (miRBase Accession No. MIMAT0031180) and homologs or orthologs from other species. The gene can be obtained by the method described in Velthut-Meikas A et al., 2013, Mol Endocrinol., 27, 1128-1141. Furthermore, a known precursor of "hsa-miR-7977" is "hsa-mir-7977" (miRBase Accession No. MI0025753, SEQ ID NO: 454), which has a hairpin-like structure.
[0283] As used herein, the term "hsa-miR-8052 gene" or "hsa-miR-8052" encompasses the hsa-miR-8052 gene set forth in SEQ ID NO: 224 (miRBase Accession No. MIMAT0030979) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock., 39, 480-487. Furthermore, "hsa-miR-8052" is known to have a precursor, "hsa-mir-8052" (miRBase Accession No. MI0025888, SEQ ID NO: 455), which has a hairpin-like structure.
[0284] As used herein, the term "hsa-miR-8069 gene" or "hsa-miR-8069" encompasses the hsa-miR-8069 gene set forth in SEQ ID NO: 225 (miRBase Accession No. MIMAT0030996) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock., 39, 480-487. Furthermore, "hsa-miR-8069" is known to have precursors with hairpin-like structures, such as "hsa-mir-8069-1" (miRBase Accession No. MI0025905, SEQ ID NO: 481) and "hsa-mir-8069-2" (miRBase Accession No. MI0031519, SEQ ID NO: 493).
[0285] As used herein, the term "hsa-miR-8073 gene" or "hsa-miR-8073" encompasses the hsa-miR-8073 gene set forth in SEQ ID NO: 226 (miRBase Accession No. MIMAT0031000) and homologs or orthologs from other species. The gene can be obtained by the method described in Wang HJ et al., 2013, Shock., 39, 480-487. Furthermore, "hsa-miR-8073" is known to have a precursor, "hsa-mir-8073" (miRBase Accession No. MI0025909, SEQ ID NO: 456), which has a hairpin-like structure.
[0286] As used herein, the term "hsa-miR-887-3p gene" or "hsa-miR-887-3p" encompasses the hsa-miR-887-3p gene set forth in SEQ ID NO: 227 (miRBase Accession No. MIMAT0004951) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Berezikov E et al., 2006, Genome Res., vol. 16, pp. 1289-1298. Furthermore, the precursor of "hsa-miR-887-3p" is known to be "hsa-mir-887" (miRBase Accession No. MI0005562, SEQ ID NO: 457), which has a hairpin-like structure.
[0287] As used herein, the terms "hsa-miR-937-5p gene" or "hsa-miR-937-5p" encompass the hsa-miR-937-5p gene set forth in SEQ ID NO: 228 (miRBase Accession No. MIMAT0022938) and homologs or orthologs from other species. The gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res., vol. 67, pp. 6031-6043. Furthermore, the precursor of "hsa-miR-937-5p" is known to be "hsa-mir-937" (miRBase Accession No. MI0005759, SEQ ID NO: 458), which has a hairpin-like structure.
[0288] As used herein, the term "hsa-miR-1202 gene" or "hsa-miR-1202" encompasses the hsa-miR-1202 gene set forth in SEQ ID NO: 229 (miRBase Accession No. MIMAT0005865) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Marton S et al., 2008, Leukemia., 22, 330-338. Furthermore, "hsa-miR-1202" is known to have a precursor, "hsa-mir-1202" (miRBase Accession No. MI0006334, SEQ ID NO: 459), which has a hairpin-like structure.
[0289] As used herein, the terms "hsa-miR-1207-5p gene" or "hsa-miR-1207-5p" encompass the hsa-miR-1207-5p gene set forth in SEQ ID NO: 230 (miRBase Accession No. MIMAT0005871) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Huppi K et al., 2008, Mol Cancer Res., 6, 212-221. Furthermore, the precursor of "hsa-miR-1207-5p" is known to be "hsa-mir-1207" (miRBase Accession No. MI0006340, SEQ ID NO: 460), which has a hairpin-like structure.
[0290] As used herein, the term "hsa-miR-1246 gene" or "hsa-miR-1246" encompasses the hsa-miR-1246 gene set forth in SEQ ID NO: 231 (miRBase Accession No. MIMAT0005898) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res., vol. 18, pp. 610-621. Furthermore, a known precursor of "hsa-miR-1246" is "hsa-mir-1246" (miRBase Accession No. MI0006381, SEQ ID NO: 461), which has a hairpin-like structure.
[0291] As used herein, the term "hsa-miR-1254 gene" or "hsa-miR-1254" encompasses the hsa-miR-1254 gene set forth in SEQ ID NO: 232 (miRBase Accession No. MIMAT0005905) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Morin RD et al., 2008, Genome Res., vol. 18, pp. 610-621. Furthermore, known precursors of "hsa-miR-1254" include "hsa-mir-1254-1" (miRBase Accession No. MI0006388, SEQ ID NO: 482) and "hsa-mir-1254-2" (miRBase Accession No. MI0016747, SEQ ID NO: 494), which have hairpin-like structures.
[0292] As used herein, the terms "hsa-miR-135a-3p gene" or "hsa-miR-135a-3p" encompass the hsa-miR-135a-3p gene set forth in SEQ ID NO: 233 (miRBase Accession No. MIMAT0004595) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr. Biol., 12, 735-739. Furthermore, "hsa-miR-135a-3p" is known to have a precursor, "hsa-mir-135a-1" (miRBase Accession No. MI0000452, SEQ ID NO: 462), which has a hairpin-like structure.
[0293] As used herein, the term "hsa-miR-1469 gene" or "hsa-miR-1469" encompasses the hsa-miR-1469 gene set forth in SEQ ID NO: 234 (miRBase Accession No. MIMAT0007347) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Kawaji H et al., 2008, BMC Genomics, 9, 157. Furthermore, "hsa-miR-1469" is known to have a precursor, "hsa-mir-1469" (miRBase Accession No. MI0007074, SEQ ID NO: 463), which has a hairpin-like structure.
[0294] As used herein, the terms "hsa-miR-149-3p gene" or "hsa-miR-149-3p" encompass the hsa-miR-149-3p gene set forth in SEQ ID NO: 235 (miRBase Accession No. MIMAT0004609) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol., 12, 735-739. Furthermore, "hsa-miR-149-3p" is known to have a precursor, "hsa-mir-149" (miRBase Accession No. MI0000478, SEQ ID NO: 464), which has a hairpin-like structure.
[0295] As used herein, the terms "hsa-miR-150-3p gene" or "hsa-miR-150-3p" encompass the hsa-miR-150-3p gene set forth in SEQ ID NO: 236 (miRBase Accession No. MIMAT0004610) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Lagos-Quintana M et al., 2002, Curr Biol., 12, 735-739. Furthermore, the precursor of "hsa-miR-150-3p" is known to be "hsa-mir-150" (miRBase Accession No. MI0000479, SEQ ID NO: 465), which has a hairpin-like structure.
[0296] As used herein, the terms "hsa-miR-1914-3p gene" or "hsa-miR-1914-3p" encompass the hsa-miR-1914-3p gene set forth in SEQ ID NO: 237 (miRBase Accession No. MIMAT0007890) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Bar M et al., 2008, Stem Cells., vol. 26, pp. 2496-2505. Furthermore, the precursor of "hsa-miR-1914-3p" is known to be "hsa-mir-1914" (miRBase Accession No. MI0008335, SEQ ID NO: 466), which has a hairpin-like structure.
[0297] As used herein, the terms "hsa-miR-191-5p gene" or "hsa-miR-191-5p" encompass the hsa-miR-191-5p gene set forth in SEQ ID NO: 238 (miRBase Accession No. MIMAT0000440) and homologs or orthologs from other species. The gene can be obtained by the method described in Lagos-Quintana M et al., 2003, RNA., 9, 175-179. Furthermore, the precursor of "hsa-miR-191-5p" is known to be "hsa-mir-191" (miRBase Accession No. MI0000465, SEQ ID NO: 467), which has a hairpin-like structure.
[0298] As used herein, the terms "hsa-miR-423-5p gene" or "hsa-miR-423-5p" encompass the hsa-miR-423-5p gene set forth in SEQ ID NO: 239 (miRBase Accession No. MIMAT0004748) as well as homologs or orthologs from other organisms. The gene can be obtained by the method described in Kasashima K et al., 2004, Biochem Biophys Res Commun., 322, 403-410. Furthermore, the precursor of "hsa-miR-423-5p" is known to be "hsa-mir-423" (miRBase Accession No. MI0001445, SEQ ID NO: 468), which has a hairpin-like structure.
[0299] As used herein, the term "hsa-miR-663a gene" or "hsa-miR-663a" encompasses the hsa-miR-663a gene set forth in SEQ ID NO: 240 (miRBase Accession No. MIMAT0003326) and homologs or orthologs from other organisms. The gene can be obtained by the method described in Cummins JM et al., 2006, Proc Natl Acad Sci U S A., vol. 103, 3687-3692. Furthermore, "hsa-miR-663a" is known to have a precursor, "hsa-mir-663a" (miRBase Accession No. MI0003672, SEQ ID NO: 469), which has a hairpin-like structure.
[0300] As used herein, the term "hsa-miR-92a-2-5p gene" or "hsa-miR-92a-2-5p" encompasses the hsa-miR-92a-2-5p gene set forth in SEQ ID NO: 241 (miRBase Accession No. MIMAT0004508) and homologs or orthologs from other species. The gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev., 16, 720-728. Furthermore, the precursor of "hsa-miR-92a-2-5p" is known to be "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 470), which has a hairpin-like structure.
[0301] As used herein, the term "hsa-miR-92a-3p gene" or "hsa-miR-92a-3p" encompasses the hsa-miR-92a-3p gene set forth in SEQ ID NO: 242 (miRBase Accession No. MIMAT0000092) and homologs or orthologs from other species. The gene can be obtained by the method described in Mourelatos Z et al., 2002, Genes Dev., vol. 16, pp. 720-728. Furthermore, known precursors of "hsa-miR-92a-3p" include "hsa-mir-92a-1" (miRBase Accession No. MI0000093, SEQ ID NO: 483) and "hsa-mir-92a-2" (miRBase Accession No. MI0000094, SEQ ID NO: 495), which have a hairpin-like structure.
[0302] As used herein, the term "hsa-miR-940 gene" or "hsa-miR-940" encompasses the hsa-miR-940 gene set forth in SEQ ID NO: 243 (miRBase Accession No. MIMAT0004983) as well as homologs or orthologs from other species. The gene can be obtained by the method described in Lui WO et al., 2007, Cancer Res., vol. 67, pp. 6031-6043. Furthermore, "hsa-miR-940" is known to have a precursor, "hsa-mir-940" (miRBase Accession No. MI0005762, SEQ ID NO: 471), which has a hairpin-like structure.
[0303] Furthermore, when mature miRNAs are excised from RNA precursors with hairpin-like structures, one to several bases before or after the sequence may be shortened or lengthened, or base substitutions may occur, resulting in mutants called isomiRs (Morin RD. et al., 2008, Genome Res., Vol. 18, pp. 610-621). In addition to the nucleotide sequences represented by any of SEQ ID NOS: 1 to 243, miRBase Release 21 also lists numerous mutants and fragments of the nucleotide sequences represented by any of SEQ ID NOS: 507 to 766, known as isomiRs. These mutants can also be obtained as miRNAs with the nucleotide sequences represented by any of SEQ ID NOS: 1 to 243. That is, SEQ ID NOs: 1, 2, 3, 8, 9, 10, 12, 13, 14, 15, 16, 17, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 42, 43, 44, 45, 46, 47, 48, 49, 51, 54, 55, 56, 58, 61, 62, 63, 67, 68, 69, 71, 72, 73, 74, 75, 77, 78, 80, 81, 82, 84, 86, 87, 89, 90, 91, 92, 93, 94, 95, 96, 101, 103, 105, 109, 111, 113, 114, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, Among variants of polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 18, 119, 123, 124, 126, 127, 129, 131, 132, 133, 134, 135, 136, 139, 142, 143, 146, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 161, 162, 163, 164, 166, 218, 221, 227, 228, 231, 232, 233, 235, 236, 237, 238, 239, 240, 241, 242, and 243, or the nucleotide sequences in which u is replaced by t, the longest variants registered in miRBase Release 21 include the polynucleotides represented by SEQ ID NOs: 507 to 632, respectively.Furthermore, SEQ ID NOs: 1, 2, 3, 4, 8, 9, 10, 12, 13, 14, 15, 16, 17, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 51, 53, 54, 55, 56, 58, 61, 62, 63, 67, 68, 71, 72, 73, 74, 75, 77, 78, 80, 81, 82, 84, 86, 90, 91, 92, 93, 95, 96, 101, 105, 107, 109, 111, 112, 113, 114, 116 , 117, 118, 119, 120, 122, 123, 124, 125, 126, 127, 129, 131, 132, 133, 134, 135, 136, 138, 139, 142, 143, 145, 146, 150, 151, 152, 154, 155, 156, 157, 158, 159, 161, 162, 163, 164, 166, 218, 221, 222, 227, 228, 229, 231, 232, 233, 235, or a polynucleotide consisting of said base sequence where u is t. For example, the shortest variants registered in miRBase Release 21 include polynucleotides having the sequences represented by SEQ ID NOs: 633 to 766, respectively. In addition to these variants and fragments, examples of polynucleotides include the numerous isomiRs registered in miRBase, represented by SEQ ID NOs: 1 to 243. Furthermore, examples of polynucleotides containing a nucleotide sequence represented by any of SEQ ID NOs: 1 to 243 include the polynucleotides represented by their respective precursors, represented by any of SEQ ID NOs: 507 to 766.
[0304] The names of the genes represented by SEQ ID NOs: 1 to 766 and their miRBase Accession Nos. (registration numbers) are shown in Table 1.
[0305] As used herein, the term "capable of specifically binding" means that the nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and is substantially incapable of binding to other nucleic acids.
[0306] [Table 1] TIFF2025179134000002.tif231103TIFF2025179134000003.tif229111TIFF2025179134000004.tif234109TIFF2025179134000005.tif233111TIFF2025179134000006.tif228107TIFF2025179134000007.tif228108TIFF2025179134000008.tif228105TIFF2025179134000009.tif230105TIFF2025179134000010.tif232113TIFF2025179134000011.tif231105TIFF2025179134000012.tif230105TIFF2025179134000013.tif229106TIFF2025179134000014.tif228106TIFF2025179134000015.tif143120
[0307] This specification includes the disclosure of Japanese Patent Application No. 2018-084416, from which the present application claims priority. [Effects of the Invention]
[0308] The present invention enables easy and highly accurate detection of bladder cancer. For example, by using the measured expression levels of one to several miRNAs in the patient's blood, serum, and / or plasma, which can be collected minimally invasively, as an indicator, it is possible to easily determine whether a patient has bladder cancer. [Brief explanation of the drawings]
[0309] [Figure 1] This figure shows the relationship between the base sequences of hsa-miR-1228-5p (represented by sequence number 9) and hsa-miR-1228-3p (represented by sequence number 8), which are generated from the precursor hsa-mir-1228 (represented by sequence number 251). [Figure 2]FIG. 2 shows a plot of the discriminant scores for a training sample group (A) and a validation sample group (B) using a discriminant equation for one miRNA. [Figure 3] FIG. 3 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant for one miRNA. [Figure 4A-B] Figures 4A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant for one miRNA. [Figure 4C-D] Figures 4C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant equation for one miRNA. [Figure 5] FIG. 5 shows plots of the discriminant scores for the training sample group (A) and the validation sample group (B) using the discriminant equations for three miRNAs. [Figure 6] FIG. 6 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for three miRNAs. [Figure 7A-B] 7A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant equations for three miRNAs. [Figure 7C-D] Figures 7C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant equation for three miRNAs. [Figure 8] FIG. 8 shows plots of the discriminant scores for the training sample group (A) and the validation sample group (B) using the discriminant equations for four miRNAs. [Figure 9] FIG. 9 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for four miRNAs. [Figure 10A-B] 10A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant equations for four miRNAs. [Figure 10C-D] Figures 10C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant equation for four miRNAs. [Figure 11] FIG. 11 shows plots of the discriminant scores for the training sample group (A) and the validation sample group (B) using the discriminant equations for five miRNAs. [Figure 12] FIG. 12 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for five miRNAs. [Figure 13A-B] 13A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant formula for five miRNAs. [Figure 13C-D] Figures 13C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant formula for five miRNAs. [Figure 14] FIG. 14 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for three miRNAs. [Figure 15A-B] 15A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant equations for three miRNAs. [Figure 15C-D] Figures 15C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant equation for three miRNAs. [Figure 16] FIG. 16 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for 10 miRNAs. [Figure 17A-B] 17A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant formula for 10 miRNAs. [Figure 17C-D] Figures 17C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant formula for 10 miRNAs. [Figure 18] FIG. 18 shows a plot of the discrimination scores by disease type for the validation sample group using the discriminant equations for 104 miRNAs. [Figure 19A-B] 19A-B show plots of the discrimination scores of the validation sample group by stage (A) and by the degree of intramural invasion (B) using the discriminant equation for 104 miRNAs. [Figure 19C-D] Figures 19C-D show discriminant score plots for the validation sample group, classified by histological grade (C) and primary / recurrent (D), using the discriminant equation for 104 miRNAs. [Figure 20]FIG. 20 shows the ROC curves for a training sample group (A) and a validation sample group (C) for one miRNA, and the ROC curves for a training sample group (B) and a validation sample group (D) for a combination of seven miRNAs. [Figure 21] FIG. 21 shows a plot of the discrimination scores by disease type for combinations of seven miRNAs. DETAILED DESCRIPTION OF THE INVENTION
[0310] The present invention will be described in more detail below. 1. Bladder cancer target nucleic acid The main target nucleic acids as bladder cancer markers for detecting the presence and / or absence of bladder cancer or bladder cancer cells using the nucleic acid probe or primer for detecting bladder cancer defined above of the present invention include miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1269a, miR-1270a, miR-1271a, miR-1272a, miR-1273a, miR-1274a, miR-1275a, miR-1276a, miR-1277a, miR-1278a, miR-1279a, miR-1280a, miR-1281a, miR-1282a, miR-1283a, miR-1284a, miR-1285a, miR-1286a, miR-1287a, miR-1288a, miR-1289a, miR-1290a, miR-1291a, miR-1292a, miR-1293a, miR-1294a, miR-1295a, miR-1296a, miR-1297a, miR-1298a, miR-1299a, miR-2000a, miR-2000a, miR-2000a, miR-2000a, mi 68b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR- 1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5 p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p , miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, mi R-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR -4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462,miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR- 4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, miR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-46 87-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722 -5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, miR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3 p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-498, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, m iR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131, miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR-6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-673 7-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760-5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3pmiR-6766-5p、miR-6771-5p、miR-6774-5p、miR-6777-5p、miR-6778-5p、miR-6780b-5p、miR-6781-5p、miR-6782-5p、mi R-6784-5p、miR-6785-5p、miR-6787-5p、miR-6789-5p、miR-6791-5p、miR-6794-5p、miR-6800-5p、miR-6802-5p、miR-6 803-5p、miR-6812-5p、miR-6816-5p、miR-6819-5p、miR-6821-5p、miR-6826-5p、miR-6831-5p、miR-6836-3p、miR-6840 -3p、miR-6842-5p、miR-6850-5p、miR-6861-5p、miR-6869-5p、miR-6870-5p、miR-6877-5p、miR-6879-5p、miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, and miR-937-5p. Furthermore, other bladder cancer markers that can be combined with these miRNAs, i.e., at least one miRNA selected from the group consisting of miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940, can also be preferably used as target nucleic acids.
[0311] The above-mentioned miRNAs include, for example, human genes containing nucleotide sequences represented by any of SEQ ID NOs: 1 to 243 (that is, miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483,miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-464 9-5p, miR-4651, miR-4652-5p, miR-4655-5p, miR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-46 95-5p, miR-4697-5p, miR-4706, miR-4707-3p, miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727 -3p, miR-4728-5p, miR-4731-5p, miR-4736, miR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, m iR-4783-5p, miR-4787-3p, miR-4792, miR-498, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-607 5, miR-6076, miR-6088, miR-6124, miR-6131, miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p miR-6515-5p miR-663b miR-6716-5p miR-6717-5p miR-6722-3p miR-6724-5p miR-6726-5p miR-6737-5p miR-6741-5p miR-6742-5p miR-674 3-5p, miR-6746-5p, miR-6749-5p, miR-6760-5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5pmiR-6777-5p, miR-6778-5p, miR-6780b-5p, miR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6 787-5p, miR-6789-5p, miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p , miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6 842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p , miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, miR- The term "gene," "homologue," "transcript," "variant," and "derivative" includes genes, homologs, transcription products, and variants or derivatives thereof, including miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940, as well as homologs, transcription products, variants, and derivatives thereof, where the terms "gene," "homologue," "transcript," "variant," and "derivative" are defined above.
[0312] Preferred target nucleic acids are human genes comprising the base sequence shown in any one of SEQ ID NOs: 1 to 243, or transcription products thereof, more preferably such transcription products, ie, miRNAs, or their precursor RNAs, pri-miRNAs or pre-miRNAs.
[0313] The first target gene is the hsa-miR-6087 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of genes or their transcription products could be markers for bladder cancer.
[0314] The second target gene is the hsa-miR-1185-1-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0315] The third target gene is the hsa-miR-1185-2-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0316] The fourth target gene is the hsa-miR-1193 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of genes or their transcripts could be markers for bladder cancer.
[0317] The fifth target gene is the hsa-miR-1199-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0318] The sixth target gene is the hsa-miR-1225-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0319] The seventh target gene is the hsa-miR-1227-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0320] The eighth target gene is the hsa-miR-1228-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0321] The ninth target gene is the hsa-miR-1228-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0322] The tenth target gene is the hsa-miR-1237-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0323] The eleventh target gene is the hsa-miR-1238-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0324] The twelfth target gene is the hsa-miR-1247-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0325] The thirteenth target gene is the hsa-miR-1268a gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0326] The 14th target gene is the hsa-miR-1268b gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0327] The 15th target gene is the hsa-miR-1273g-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0328] The 16th target gene is the hsa-miR-128-2-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0329] The 17th target gene is the hsa-miR-1343-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0330] The 18th target gene is the hsa-miR-1343-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0331] The 19th target gene is the hsa-miR-1470 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0332] The 20th target gene is the hsa-miR-17-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0333] The 21st target gene is the hsa-miR-187-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0334] The 22nd target gene is the hsa-miR-1908-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0335] The 23rd target gene is the hsa-miR-1908-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0336] The 24th target gene is the hsa-miR-1909-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0337] The 25th target gene is the hsa-miR-1915-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0338] The 26th target gene is the hsa-miR-210-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0339] The 27th target gene is the hsa-miR-24-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0340] The 28th target gene is the hsa-miR-2467-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0341] The 29th target gene is the hsa-miR-2861 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0342] The 30th target gene is the hsa-miR-296-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0343] The 31st target gene is the hsa-miR-29b-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0344] The 32nd target gene is the hsa-miR-3131 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0345] The 33rd target gene is the hsa-miR-3154 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0346] The 34th target gene is the hsa-miR-3158-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0347] The 35th target gene is the hsa-miR-3160-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0348] The 36th target gene is the hsa-miR-3162-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0349] The 37th target gene is the hsa-miR-3178 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0350] The 38th target gene is the hsa-miR-3180-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0351] The 39th target gene is the hsa-miR-3184-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0352] The 40th target gene is the hsa-miR-3185 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0353] The 41st target gene is the hsa-miR-3194-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0354] The 42nd target gene is the hsa-miR-3195 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0355] The 43rd target gene is the hsa-miR-3197 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0356] The 44th target gene is the hsa-miR-320a gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0357] The 45th target gene is the hsa-miR-320b gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0358] The 46th target gene is the hsa-miR-328-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0359] The 47th target gene is the hsa-miR-342-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0360] The 48th target gene is the hsa-miR-345-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0361] The 49th target gene is the hsa-miR-3616-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0362] The 50th target gene is the hsa-miR-3619-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0363] The 51st target gene is the hsa-miR-3620-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0364] The 52nd target gene is the hsa-miR-3621 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0365] The 53rd target gene is the hsa-miR-3622a-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0366] The 54th target gene is the hsa-miR-3648 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0367] The 55th target gene is the hsa-miR-3652 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0368] The 56th target gene is the hsa-miR-3656 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0369] The 57th target gene is the hsa-miR-3663-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0370] The 58th target gene is the hsa-miR-3679-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0371] The 59th target gene is the hsa-miR-371b-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0372] The 60th target gene is the hsa-miR-373-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0373] The 61st target gene is the hsa-miR-3917 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0374] The 62nd target gene is the hsa-miR-3940-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0375] The 63rd target gene is the hsa-miR-3960 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0376] The 64th target gene is the hsa-miR-4258 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0377] The 65th target gene is the hsa-miR-4259 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0378] The 66th target gene is the hsa-miR-4270 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0379] The 67th target gene is the hsa-miR-4286 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0380] The 68th target gene is the hsa-miR-4298 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0381] The 69th target gene is the hsa-miR-4322 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0382] The 70th target gene is the hsa-miR-4327 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0383] The 71st target gene is the hsa-miR-4417 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0384] The 72nd target gene is the hsa-miR-4419b gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0385] The 73rd target gene is the hsa-miR-4429 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0386] The 74th target gene is the hsa-miR-4430 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0387] The 75th target gene is the hsa-miR-4433a-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0388] The 76th target gene is the hsa-miR-4436b-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0389] The 77th target gene is the hsa-miR-4443 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0390] The 78th target gene is the hsa-miR-4446-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0391] The 79th target gene is the hsa-miR-4447 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0392] The 80th target gene is the hsa-miR-4448 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0393] The 81st target gene is the hsa-miR-4449 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0394] The 82nd target gene is the hsa-miR-4454 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0395] The 83rd target gene is the hsa-miR-4455 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0396] The 84th target gene is the hsa-miR-4459 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0397] The 85th target gene is the hsa-miR-4462 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0398] The 86th target gene is the hsa-miR-4466 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0399] The 87th target gene is the hsa-miR-4467 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0400] The 88th target gene is the hsa-miR-4480 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0401] The 89th target gene is the hsa-miR-4483 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0402] The 90th target gene is the hsa-miR-4484 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0403] The 91st target gene is the hsa-miR-4485-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0404] The 92nd target gene is the hsa-miR-4488 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0405] The 93rd target gene is the hsa-miR-4492 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0406] The 94th target gene is the hsa-miR-4505 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0407] The 95th target gene is the hsa-miR-4515 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0408] The 96th target gene is the hsa-miR-4525 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0409] The 97th target gene is the hsa-miR-4534 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0410] The 98th target gene is the hsa-miR-4535 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0411] The 99th target gene is the hsa-miR-4633-3p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0412] The 100th target gene is the hsa-miR-4634 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0413] The 101st target gene is the hsa-miR-4640-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0414] The 102nd target gene is the hsa-miR-4649-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0415] The 103rd target gene is the hsa-miR-4651 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0416] The 104th target gene is the hsa-miR-4652-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0417] The 105th target gene is the hsa-miR-4655-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0418] The 106th target gene is the hsa-miR-4656 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0419] The 107th target gene is the hsa-miR-4658 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0420] The 108th target gene is the hsa-miR-4663 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0421] The 109th target gene is the hsa-miR-4673 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0422] The 110th target gene is the hsa-miR-4675 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0423] The 111th target gene is the hsa-miR-4687-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0424] The 112th target gene is the hsa-miR-4687-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0425] The 113th target gene is the hsa-miR-4690-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0426] The 114th target gene is the hsa-miR-4695-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0427] The 115th target gene is the hsa-miR-4697-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0428] The 116th target gene is the hsa-miR-4706 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0429] The 117th target gene is the hsa-miR-4707-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0430] The 118th target gene is the hsa-miR-4707-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0431] The 119th target gene is the hsa-miR-4708-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0432] The 120th target gene is the hsa-miR-4710 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0433] The 121st target gene is the hsa-miR-4718 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0434] The 122nd target gene is the hsa-miR-4722-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0435] The 123rd target gene is the hsa-miR-4725-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0436] The 124th target gene is the hsa-miR-4726-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0437] The 125th target gene is the hsa-miR-4727-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0438] The 126th target gene is the hsa-miR-4728-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0439] The 127th target gene is the hsa-miR-4731-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0440] The 128th target gene is the hsa-miR-4736 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0441] The 129th target gene is the hsa-miR-4739 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0442] The 130th target gene is the hsa-miR-4740-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0443] The 131st target gene is the hsa-miR-4741 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0444] The 132nd target gene is the hsa-miR-4750-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0445] The 133rd target gene is the hsa-miR-4755-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0446] The 134th target gene is the hsa-miR-4763-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0447] The 135th target gene is the hsa-miR-4771 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0448] The 136th target gene is the hsa-miR-4783-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0449] The 137th target gene is the hsa-miR-4783-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0450] The 138th target gene is the hsa-miR-4787-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0451] The 139th target gene is the hsa-miR-4792 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0452] The 140th target gene is the hsa-miR-498 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0453] The 141st target gene is the hsa-miR-5008-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0454] The 142nd target gene is the hsa-miR-5010-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0455] The 143rd target gene is the hsa-miR-504-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0456] The 144th target gene is the hsa-miR-5195-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0457] The 145th target gene is the hsa-miR-550a-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0458] The 146th target gene is the hsa-miR-5572 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0459] The 147th target gene is the hsa-miR-5739 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0460] The 148th target gene is the hsa-miR-6075 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0461] The 149th target gene is the hsa-miR-6076 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0462] The 150th target gene is the hsa-miR-6088 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0463] The 151st target gene is the hsa-miR-6124 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0464] The 152nd target gene is the hsa-miR-6131 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0465] The 153rd target gene is the hsa-miR-6132 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0466] The 154th target gene is the hsa-miR-614 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0467] The 155th target gene is the hsa-miR-615-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0468] The 156th target gene is the hsa-miR-619-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0469] The 157th target gene is the hsa-miR-642b-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0470] The 158th target gene is the hsa-miR-6510-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0471] The 159th target gene is the hsa-miR-6511a-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0472] The 160th target gene is the hsa-miR-6515-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0473] The 161st target gene is the hsa-miR-6515-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0474] The 162nd target gene is the hsa-miR-663b gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0475] The 163rd target gene is the hsa-miR-6716-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0476] The 164th target gene is the hsa-miR-6717-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0477] The 165th target gene is the hsa-miR-6722-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0478] The 166th target gene is the hsa-miR-6724-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0479] The 167th target gene is the hsa-miR-6726-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0480] The 168th target gene is the hsa-miR-6737-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0481] The 169th target gene is the hsa-miR-6741-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0482] The 170th target gene is the hsa-miR-6742-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0483] The 171st target gene is the hsa-miR-6743-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0484] The 172nd target gene is the hsa-miR-6746-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0485] The 173rd target gene is the hsa-miR-6749-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0486] The 174th target gene is the hsa-miR-6760-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0487] The 175th target gene is the hsa-miR-6762-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0488] The 176th target gene is the hsa-miR-6765-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0489] The 177th target gene is the hsa-miR-6765-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0490] The 178th target gene is the hsa-miR-6766-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0491] The 179th target gene is the hsa-miR-6766-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0492] The 180th target gene is the hsa-miR-6771-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0493] The 181st target gene is the hsa-miR-6774-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0494] The 182nd target gene is the hsa-miR-6777-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0495] The 183rd target gene is the hsa-miR-6778-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0496] The 184th target gene is the hsa-miR-6780b-5p gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0497] The 185th target gene is the hsa-miR-6781-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0498] The 186th target gene is the hsa-miR-6782-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0499] The 187th target gene is the hsa-miR-6784-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0500] The 188th target gene is the hsa-miR-6785-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0501] The 189th target gene is the hsa-miR-6787-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0502] The 190th target gene is the hsa-miR-6789-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0503] The 191st target gene is the hsa-miR-6791-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0504] The 192nd target gene is the hsa-miR-6794-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0505] The 193rd target gene is the hsa-miR-6800-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0506] The 194th target gene is the hsa-miR-6802-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0507] The 195th target gene is the hsa-miR-6803-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0508] The 196th target gene is the hsa-miR-6812-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0509] The 197th target gene is the hsa-miR-6816-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0510] The 198th target gene is the hsa-miR-6819-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0511] The 199th target gene is the hsa-miR-6821-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0512] The 200th target gene is the hsa-miR-6826-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0513] The 201st target gene is the hsa-miR-6831-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0514] The 202nd target gene is the hsa-miR-6836-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0515] The 203rd target gene is the hsa-miR-6840-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0516] The 204th target gene is the hsa-miR-6842-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0517] The 205th target gene is the hsa-miR-6850-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0518] The 206th target gene is the hsa-miR-6861-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0519] The 207th target gene is the hsa-miR-6869-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0520] The 208th target gene is the hsa-miR-6870-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0521] The 209th target gene is the hsa-miR-6877-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0522] The 210th target gene is the hsa-miR-6879-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0523] The 211th target gene is the hsa-miR-6880-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0524] The 212th target gene is the hsa-miR-6880-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0525] The 213th target gene is the hsa-miR-6885-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0526] The 214th target gene is the hsa-miR-6887-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0527] The 215th target gene is the hsa-miR-7107-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0528] The 216th target gene is the hsa-miR-7108-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0529] The 217th target gene is the hsa-miR-7109-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of genes or their transcription products could be markers for bladder cancer.
[0530] The 218th target gene is the hsa-miR-711 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0531] The 219th target gene is the hsa-miR-7113-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0532] The 220th target gene is the hsa-miR-7150 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0533] The target gene of miR-221 is the hsa-miR-744-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0534] The target gene of miR-222 is the hsa-miR-7975 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0535] The 223rd target gene is the hsa-miR-7977 gene, its homologs, its transcripts, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcripts could be a marker for bladder cancer.
[0536] The 224th target gene is the hsa-miR-8052 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0537] The 225th target gene is the hsa-miR-8069 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products could be a marker for bladder cancer.
[0538] The 226th target gene is the hsa-miR-8073 gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of genes or their transcription products could be markers for bladder cancer.
[0539] The 227th target gene is the hsa-miR-887-3p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0540] The 228th target gene is the hsa-miR-937-5p gene, its homologs, its transcription products, or their mutants or derivatives. There have been no reports to date that altered expression of the gene or its transcription products can be a marker for bladder cancer.
[0541] The 229th target gene is the miR-1202 gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0542] The 230th target gene is the miR-1207-5p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of genes or their transcription products can be markers for bladder cancer (Patent Document 1).
[0543] The 231st target gene is the miR-1246 gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 2).
[0544] The 232nd target gene is the miR-1254 gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of genes or their transcription products can be markers for bladder cancer (Patent Document 2).
[0545] The 233rd target gene is the miR-135a-3p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0546] The 234th target gene is the miR-1469 gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0547] The 235th target gene is the miR-149-3p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0548] The 236th target gene is the miR-150-3p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of genes or their transcription products can be markers for bladder cancer (Patent Document 1).
[0549] The 237th target gene is the miR-1914-3p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of genes or their transcription products can be markers for bladder cancer (Patent Document 1).
[0550] The 238th target gene is the miR-191-5p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of genes or their transcription products can be markers for bladder cancer (Non-Patent Document 2).
[0551] The 239th target gene is the miR-423-5p gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of genes or their transcription products can be markers for bladder cancer (Non-Patent Document 3).
[0552] The 240th target gene is the miR-663a gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0553] The 241st target gene is the miR-92a-2-5p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 1).
[0554] The 242nd target gene is the miR-92a-3p gene, its homologs, its transcription products, or their mutants or derivatives. It has been reported that changes in the expression of the gene or its transcription products can be markers for bladder cancer (Patent Document 2).
[0555] The 243rd target gene is the miR-940 gene, its homologs, its transcription products, or their mutants or derivatives. Previous reports have suggested that changes in the expression of genes or their transcription products can be markers for bladder cancer (Non-Patent Document 2).
[0556] In one aspect, the present invention relates to a marker for detecting or diagnosing bladder cancer, which comprises at least one of the above-mentioned target nucleic acids.
[0557] In one aspect, the present invention relates to the use of at least one of the above target nucleic acids for detecting or diagnosing bladder cancer.
[0558] 2. Nucleic acid probes or primers for detecting bladder cancer In the present invention, nucleic acid probes or primers that can be used to detect or diagnose bladder cancer include human-derived miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, and miR-1273h-3p. p、miR-128-2-5p、miR-1343-3p、miR-1343-5p、miR-1470、miR-17-3p、miR-187-5p、miR-1908-3p、miR-1908-5p、miR-1909-3p、miR-1915-3p、miR-210 -5p、miR-24-3p、miR-2467-3p、miR-2861、miR-296-3p、miR-29b-3p、miR-3131、miR-3154、miR-3158-5p、miR-3160-5p、miR-3162-5p、miR-3178、miR-3 180-3p、miR-3184-5p、miR-3185、miR-3194-3p、miR-3195、miR-3197、miR-320a、miR-320b、miR-328-5p、miR-342-5p、miR-345-3p、miR-3616-3p、miR -3619-3p、miR-3620-5p、miR-3621、miR-3622a-5p、miR-3648、miR-3652、miR-3656、miR-3663-3p、miR-3679-5p、miR-371b-5p、miR-373-5p、miR-3917 、miR-3940-5p、miR-3960、miR-4258、miR-4259、miR-4270、miR-4286、miR-4298、miR-4322、miR-4327、miR-4417、miR-4419b、miR-4429、miR-4430、miR -4433a-3p、miR-4436b-5p、miR-4443、miR-4446-3p、miR-4447、miR-4448、miR-4449、miR-4454、miR-4455、miR-4459、miR-4462、miR-4466、miR-4467、miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, m iR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, miR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p miR-4690-5p miR-4695-5p miR-4697-5p miR-4706 miR-4707-3p miR-4707-5p miR-4708-3p miR-4710 miR-4718 miR-4722-5p miR-4725-3p miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, miR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, m iR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-498, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR- 5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131, miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, mi R-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR-6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741 -5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760-5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5pmiR-6771-5p、miR-6774-5p、miR-6777-5p、miR-6778-5p、miR-6780b-5p、miR-6781-5p、miR-6782-5p、miR-6784-5p 、miR-6785-5p、miR-6787-5p、miR-6789-5p、miR-6791-5p、miR-6794-5p、miR-6800-5p、miR-6802-5p、miR-6803-5p 、miR-6812-5p、miR-6816-5p、miR-6819-5p、miR-6821-5p、miR-6826-5p、miR-6831-5p、miR-6836-3p、miR-6840-3p , miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, or combinations thereof, their homologs, their transcription products, or their mutants or derivatives, can be measured qualitatively and / or quantitatively.
[0559] The expression levels of some of the above target nucleic acids are increased or decreased depending on the type of target nucleic acid in subjects with bladder cancer compared to healthy individuals, patients with benign diseases, and subjects with cancers other than bladder cancer (hereinafter referred to as "increase / decrease"). Therefore, the kit or device of the present invention can be effectively used to detect bladder cancer by measuring the expression levels of the above target nucleic acids in body fluids derived from subjects (e.g., humans) suspected of having bladder cancer and body fluids derived from healthy individuals, patients with benign diseases, and patients with cancers other than bladder cancer, and comparing the results.
[0560] The nucleic acid probe or primer that can be used in the present invention is a polynucleotide consisting of at least one of the nucleotide sequences represented by SEQ ID NOs: 1 to 228, or a nucleic acid probe that can specifically bind to a complementary strand of the polynucleotide, or a primer for amplifying a polynucleotide consisting of at least one of the nucleotide sequences represented by SEQ ID NOs: 1 to 228.
[0561] The nucleic acid probe or primer that can be used in the present invention may further include a polynucleotide consisting of at least one of the base sequences represented by SEQ ID NOs: 229 to 243, or a nucleic acid probe that can specifically bind to a complementary strand of the polynucleotide, or a primer for amplifying a polynucleotide consisting of at least one of the base sequences represented by SEQ ID NOs: 229 to 243.
[0562] In a preferred embodiment of the method of the present invention, the nucleic acid probe or primer comprises a combination of one or more polynucleotides selected from the group of polynucleotides containing a base sequence represented by any one of SEQ ID NOS: 1 to 766 or a base sequence in which u is replaced by t, and complementary polynucleotides thereof; polynucleotides and complementary polynucleotides thereof that hybridize under stringent conditions (described below) with DNA consisting of a base sequence complementary to the base sequence; and polynucleotides containing 15 or more, preferably 17 or more consecutive bases in the base sequence of the polynucleotides. These polynucleotides can be used as nucleic acid probes and primers for detecting the target nucleic acid, i.e., the bladder cancer marker.
[0563] More specifically, examples of nucleic acid probes or primers that can be used in the present invention are one or more polynucleotides selected from the group consisting of any of the following polynucleotides (a) to (e):
[0564] (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228 or a nucleotide sequence in which u is replaced with t, or a variant or derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence complementary to the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence; and (e) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d).
[0565] The nucleic acid probe or primer usable in the present invention can further contain, in addition to at least one polynucleotide selected from any of the polynucleotides (a) to (e) above, any of the polynucleotides (f) to (j) below.
[0566] (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 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 comprising a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243; (h) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence complementary to the base sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence; and (j) A polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i).
[0567] The above polynucleotides or fragments thereof used in the present invention may be either DNA or RNA.
[0568] The above-mentioned polynucleotides that can be used in the present invention can be prepared using common techniques such as DNA recombinant technology, PCR, and methods using automated DNA / RNA synthesizers.
[0569] DNA recombinant DNA technology and PCR method can be used, for example, the techniques described in Ausubel et al., Current Protocols in Molecular Biology, John Willey & Sons, US (1993); Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, US (1989).
[0570] Human-derived miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, represented by Array Numbers 1 to 243miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, m iR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, m iR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-49 8, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131 miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR- 6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760 -5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5pmiR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791 -5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6 819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6842-5p, mi R-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113- 3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, m iR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940 are known, and as described above, methods for obtaining them are also known. Therefore, by cloning these genes, polynucleotides usable as nucleic acid probes or primers in the present invention can be prepared.
[0571] Such nucleic acid probes or primers can be chemically synthesized using an automated DNA synthesizer. The phosphoramidite method is generally used for this synthesis, and this method allows automated synthesis of single-stranded DNA up to about 100 bases. Automated DNA synthesizers are commercially available from, for example, Polygen, ABI, and Applied BioSystems.
[0572] Alternatively, the polynucleotides of the present invention can be prepared by cDNA cloning techniques, such as the microRNA Cloning Kit Wako.
[0573] Here, the sequences of nucleic acid probes and primers for detecting polynucleotides consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 243 do not exist in vivo as miRNA or its precursor. For example, the nucleotide sequences represented by SEQ ID NOs: 9 and 8 are generated from a precursor represented by SEQ ID NO: 251, but this precursor has a hairpin-like structure as shown in FIG. 1, and the nucleotide sequences represented by SEQ ID NOs: 9 and 8 have mismatched sequences with each other. Therefore, a nucleotide sequence completely complementary to the nucleotide sequence represented by SEQ ID NO: 9 or 8 is not naturally generated in vivo. Therefore, nucleic acid probes and primers for detecting a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 243 may have an artificial nucleotide sequence that does not exist in vivo.
[0574] 3. Bladder cancer detection kit or device The present invention also provides a kit or device for detecting bladder cancer, which comprises one or more polynucleotides (which may include mutants, fragments, or derivatives) that can be used as nucleic acid probes or primers in the present invention for measuring target nucleic acids that are bladder cancer markers.
[0575] The target nucleic acid that is a bladder cancer marker in the present invention is preferably selected from Group A below. Group A: miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-12 38-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-190 8-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, m iR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-36 63-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322 miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR- 4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505, miR-4515miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, miR-4656, miR-4658 miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p, miR-4707-5p, miR- 4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, miR-4739, miR-4740 -5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-498, miR-5008-5p, m iR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131, miR-6132, miR-6 14, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR-6717-5p, miR-6 722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760-5p, miR-6762- 5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5p, miR-6781-5pmiR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791-5p, miR-6 794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p , miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6842-5p, miR-6 850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113- 3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p. ,
[0576] The additional target nucleic acid that may optionally be used for measurement is preferably selected from Group B below. Group B: miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150 -3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, miR-940.
[0577] The kit or device of the present invention comprises a nucleic acid capable of specifically binding to a target nucleic acid that is a bladder cancer marker, preferably one or more polynucleotides or variants thereof selected from the polynucleotides described in 2 above.
[0578] Specifically, the kit or device of the present invention may include at least one polynucleotide containing (or consisting of) a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence, a polynucleotide containing (or consisting of) a complementary sequence thereof, a polynucleotide that hybridizes to these polynucleotides under stringent conditions, or a mutant or fragment containing 15 or more consecutive bases of these polynucleotide sequences.
[0579] The kit or device of the present invention may further comprise one or more polynucleotides containing (or consisting of) a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in said base sequence, polynucleotides containing (or consisting of) a complementary sequence thereof, polynucleotides that hybridize to these polynucleotides under stringent conditions, or mutants or fragments containing 15 or more consecutive bases of these polynucleotide sequences.
[0580] 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 (1) and (2) below: (1) A polynucleotide containing 15 or more consecutive bases in a base sequence in which u is t in the base sequence represented by any of SEQ ID NOs: 1 to 228, or in its complementary sequence. (2) A polynucleotide comprising 15 or more consecutive bases in a base sequence represented by any one of SEQ ID NOs: 229 to 243 in which u is t or a complementary sequence thereof.
[0581] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes to such a polynucleotide under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0582] In a preferred embodiment, the polynucleotide is a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence, a polynucleotide consisting of a complementary sequence thereof, a polynucleotide that hybridizes to such a polynucleotide under stringent conditions, or a variant thereof containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0583] In a preferred embodiment, the fragment may be a polynucleotide containing 15 or more, preferably 17 or more, more preferably 19 or more consecutive bases.
[0584] In the present invention, the size of a polynucleotide fragment is, for example, the number of consecutive bases in the base sequence of each polynucleotide, ranging from 15 to less than the total number of bases in the sequence, from 17 to less than the total number of bases in the sequence, or from 19 to less than the total number of bases in the sequence.
[0585] The above-mentioned polynucleotides as target nucleic acids in the kits or devices of the present invention can be, specifically, one of the above-mentioned polynucleotides consisting of the base sequences represented by SEQ ID NOs: 1 to 243 shown in Table 1, or a combination of two, three, four, five, six, seven, eight, nine, ten or more of the above-mentioned polynucleotides, but these are merely examples, and all other various possible combinations are intended to be encompassed by the present invention.
[0586] For example, combinations of target nucleic acids in kits or devices of the present invention for distinguishing bladder cancer patients from subjects not affected by bladder cancer, such as healthy individuals, patients with benign bone and soft tissue tumors and benign breast diseases, and patients with cancers other than bladder cancer, include combinations of two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by the SEQ ID NOs: 1 to 243. Specifically, any two or more of the above-mentioned polynucleotides consisting of the nucleotide sequences represented by SEQ ID NOs: 1 to 243 may be combined. Of these, it is preferable to select at least one newly discovered polynucleotide consisting of the nucleotide sequence represented by SEQ ID NOs: 1 to 228. Of these, combinations containing at least one polynucleotide selected from the group consisting of polynucleotides listed in any of Tables 20 to 22, more preferably the group consisting of polynucleotides listed in Table 23, are particularly preferred.
[0587] Below, 253 examples are given in Table 7-Nos. 1 to 11, Table 13 to 16, and Table 26-Nos. 2 to 9 (256 discriminants are listed in the tables) as non-limiting examples of polynucleotides containing the base sequence represented by SEQ ID NO: 1 (miR-6087) or its complementary sequence, or combinations containing the same, as shown in the Examples below.
[0588] In addition to the polynucleotides of the present invention described above (which may include mutants, fragments, or derivatives), the kits or devices of the present invention may also include known polynucleotides or polynucleotides that will be discovered in the future that enable the detection of bladder cancer.
[0589] In addition to the polynucleotide of the present invention described above, the kit or device of the present invention may also contain antibodies for measuring known bladder cancer testing markers, such as the NMP22 test, which detects the nuclear matrix protein NuMA, and the BTAtrak test, which detects a specific basement membrane fragment complex.
[0590] The polynucleotides, and variants or fragments thereof, contained in the kit of the present invention may be packaged in different containers individually or in any combination.
[0591] The kit of the present invention may include a kit for extracting nucleic acid (for example, total RNA) from body fluids, cells or tissues, a fluorescent labeling substance, an enzyme and medium for amplifying nucleic acid, instructions for use, and the like.
[0592] The device of the present invention is a device for measuring a cancer marker, in which a nucleic acid such as the polynucleotide of the present invention described above, a mutant thereof, a derivative thereof, or a fragment thereof is bound or attached to a solid phase. Examples of materials for the solid phase include plastic, paper, glass, silicon, etc., and plastic is a preferred solid phase material due to its ease of processing. The shape of the solid phase is arbitrary, for example, square, round, strip, film, etc. The device of the present invention includes, for example, a device for measurement by hybridization technology, and specific examples include a blotting device and a nucleic acid array (e.g., a microarray, a DNA chip, an RNA chip, etc.).
[0593] Nucleic acid array technology is a technique in which nucleic acids are spotted onto the surface of a solid phase that has been subjected to surface treatment such as L-lysine coating or the introduction of functional groups such as amino groups or carboxyl groups as necessary, using a high-density dispenser called a spotter or arrayer, or by spraying nucleic acids onto the solid phase using an inkjet that ejects tiny droplets from a nozzle using a piezoelectric element, or by sequentially synthesizing nucleotides on the solid phase, to create an array such as a chip by binding or attaching the above nucleic acids one by one, and then using this array to measure target nucleic acids by utilizing hybridization.
[0594] The kit or device of the present invention comprises a nucleic acid capable of specifically binding to at least one, preferably at least two, more preferably at least three, and most preferably at least five to all of the polynucleotides of the miRNAs that are bladder cancer markers in Group A. The kit or device of the present invention may further comprise, as needed, a nucleic acid capable of specifically binding to at least one, preferably at least two, more preferably at least three, and most preferably at least five to all of the polynucleotides of the miRNAs that are bladder cancer markers in Group B, or to each of the complementary strands of the polynucleotides.
[0595] The kit or device of the present invention can be used for the detection of bladder cancer as described below in 4.
[0596] 4. Bladder cancer detection methods The present invention further relates to miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505 in a samplemiR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, miR-4656, m iR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p, miR-4707- 5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, miR-4739, mi R-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-498, miR-5008 -5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131, miR-6132, mi R-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR-6717-5p, miR -6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760-5p, miR-6762 -5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5p, miR-6781-5pmiR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791-5p, miR-6 794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p , miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6842-5p, miR-6 850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, and the expression levels of genes derived from bladder cancer. The present invention relates to a method for detecting bladder cancer, which method comprises measuring in vitro the expression levels (e.g., expression profiles) of one or more of the bladder cancer-derived genes represented by miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940, and using the measured expression levels (and optionally similarly measured control expression levels from healthy individuals) to assess in vitro whether a subject is affected with bladder cancer. In this method, for example, samples such as blood, serum, and plasma are collected from a subject suspected of having bladder cancer and a subject not having bladder cancer. The expression level of the gene in the sample is compared with the control expression level from a subject not having bladder cancer (e.g., by comparing the two expression levels), and if there is a difference in the expression level of the target nucleic acid in the sample, the subject can be evaluated as having bladder cancer.
[0597] The above-described method of the present invention enables early diagnosis of bladder cancer with high sensitivity and specificity in a minimally invasive manner, thereby leading to early treatment and improved prognosis, and further enabling monitoring of disease progression and the effectiveness of surgical, radiotherapeutic, and chemotherapeutic treatments.
[0598] The method for extracting bladder cancer-derived genes from blood, serum, plasma, or other samples of the present invention is particularly preferably prepared by adding the RNA extraction reagent in the 3D-Gene® RNA extraction reagent from liquid sample kit (Toray Industries, Inc.). However, the general acid phenol method (Acid Guanidinium-Phenol-Chloroform (AGPC) method) or Trizol® (Life Technologies) may also be used, or RNA extraction reagents containing acid phenol such as Trizol (Life Technologies) or Isogen (Nippon Gene) may also be used. Furthermore, kits such as the miRNeasy® Mini Kit (Qiagen) can also be used, but methods are not limited to these.
[0599] The present invention also provides a use for the in vitro detection of expression products of bladder cancer-derived miRNA genes in a specimen derived from a subject.
[0600] The method of the present invention is not limited to a specific method, and can be carried out, for example, using the kit or device of the present invention (containing the above-described nucleic acid usable in the present invention) described in 3. In this method, the kit or device used contains the polynucleotides usable in the present invention, as described above, either singly or in any possible combination.
[0601] In the detection or (genetic) diagnosis of bladder cancer of the present invention, the polynucleotides contained in the kit or device of the present invention can be used as probes or primers. When used as primers, methods such as Life Technologies' TaqMan® MicroRNA Assays and Qiagen's miScript PCR System can be used, but are not limited to these.
[0602] In the method of the present invention, measurement of gene expression levels can be performed according to standard procedures using known methods for specifically detecting specific genes, such as hybridization techniques such as Northern blotting, Southern blotting, in situ hybridization, Northern hybridization, and Southern hybridization, quantitative amplification techniques such as quantitative RT-PCR, and next-generation sequencer methods. The sample to be measured is a body fluid, such as blood, serum, plasma, or urine, collected from the subject, depending on the type of detection method used. Alternatively, total RNA prepared from such body fluids by the above-mentioned methods may be used, or various polynucleotides, including cDNA, prepared from the RNA may be used.
[0603] The methods of the present invention are useful for diagnosing bladder cancer or detecting the presence or absence of bladder cancer. Specifically, the detection of bladder cancer of the present invention can be carried out in vitro using blood, serum, plasma, urine, or other samples from a subject suspected of having bladder cancer, for example, by detecting the expression level of a gene detected by a nucleic acid probe or primer included in a kit or device of the present invention. If the expression level of a polynucleotide consisting of at least one of the nucleotide sequences represented by SEQ ID NOs: 1 to 228, and optionally one or more of the nucleotide sequences represented by SEQ ID NOs: 229 to 243, in a sample such as blood, serum, plasma, or urine from a subject suspected of having bladder cancer is statistically significantly higher than the expression level of the polynucleotide in a sample such as blood, serum, plasma, or urine from a subject not suffering from bladder cancer, the subject can be evaluated as having bladder cancer.
[0604] In the methods of the present invention, a method for detecting the absence or presence of bladder cancer in a sample derived from a subject involves collecting a body fluid, such as blood, serum, plasma, or urine, from the subject and measuring the expression level of a target gene (or target nucleic acid) contained therein using one or more polynucleotides (including mutants, fragments, or derivatives) selected from the group of polynucleotides of the present invention, thereby assessing the presence or absence of bladder cancer or detecting bladder cancer. Furthermore, the bladder cancer detection method of the present invention can also be used to assess or diagnose the presence or absence of improvement in a bladder cancer patient when a known or developmental bladder cancer-related therapeutic drug (including, but not limited to, gemcitabine, platinum compounds (cisplatin / carboplatin), paclitaxel, methotrexate, vinblastine, adriamycin, cisplatin, taxanes (docetaxel), isofamide, other platinum compounds (nedaplatin), and combinations thereof) is administered for the purpose of treating or ameliorating the disease.
[0605] The method of the present invention includes, for example, the following steps (a), (b) and (c): (a) contacting a specimen from a subject in vitro with a polynucleotide of the kit or device of the present invention; (b) measuring the expression level of the target nucleic acid in a sample using the polynucleotide as a nucleic acid probe or primer; (c) assessing the presence or absence of bladder cancer (cells) in the subject based on the results of (b); may include:
[0606] In one embodiment, the present invention relates to miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492,miR-4505, miR-4515, miR-4525, miR-4534, miR-4535, miR-4633-3p, miR-4634, miR-4640-5p, miR-4649-5p, miR-4651, miR-4652-5p, miR-4655-5p, m iR-4656, miR-4658, miR-4663, miR-4673, miR-4675, miR-4687-3p, miR-4687-5p, miR-4690-5p, miR-4695-5p, miR-4697-5p, miR-4706, miR-4707-3p miR-4707-5p, miR-4708-3p, miR-4710, miR-4718, miR-4722-5p, miR-4725-3p, miR-4726-5p, miR-4727-3p, miR-4728-5p, miR-4731-5p, miR-4736, m iR-4739, miR-4740-5p, miR-4741, miR-4750-5p, miR-4755-3p, miR-4763-3p, miR-4771, miR-4783-3p, miR-4783-5p, miR-4787-3p, miR-4792, miR-49 8, miR-5008-5p, miR-5010-5p, miR-504-3p, miR-5195-3p, miR-550a-5p, miR-5572, miR-5739, miR-6075, miR-6076, miR-6088, miR-6124, miR-6131 miR-6132, miR-614, miR-615-5p, miR-619-5p, miR-642b-3p, miR-6510-5p, miR-6511a-5p, miR-6515-3p, miR-6515-5p, miR-663b, miR-6716-5p, miR- 6717-5p, miR-6722-3p, miR-6724-5p, miR-6726-5p, miR-6737-5p, miR-6741-5p, miR-6742-5p, miR-6743-5p, miR-6746-5p, miR-6749-5p, miR-6760 -5p, miR-6762-5p, miR-6765-3p, miR-6765-5p, miR-6766-3p, miR-6766-5p, miR-6771-5p, miR-6774-5p, miR-6777-5p, miR-6778-5p, miR-6780b-5pmiR-6781-5p, miR-6782-5p, miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791 -5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6 819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR-6840-3p, miR-6842-5p, mi R-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-6880-3p , miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, and miR-937-5p, or nucleic acids capable of specifically binding to the complementary strands of said polynucleotides, and the expression level of the target nucleic acid in a specimen from a subject is measured, and whether or not the subject is affected by bladder cancer is determined based on the measured expression level and a control expression level similarly measured in a subject not affected by bladder cancer. The present invention provides a method for detecting bladder cancer, which includes evaluating in vitro.
[0607] In this specification, "evaluation" refers to evaluation support based on the results of in vitro tests, not on the judgment of a doctor.
[0608] As described above, in the method of the present invention, specifically, miR-6087 is hsa-miR-6087, miR-1185-1-3p is hsa-miR-1185-1-3p, miR-1185-2-3p is hsa-miR-1185-2-3p, miR-1193 is hsa-miR-1193, miR-1199-5p is hsa-miR-1199-5p, miR-1225-5p is hsa-miR-1225-5p, miR-1227-5p is hsa-miR-1227-5p, and miR-1228-3p is hsa-miR-1228-3p, miR-1228-5p, hsa-miR-1228-5p, miR-1237-5p, hsa-miR-1237-5p, miR-1238-5p, hsa-miR-1238-5p, miR-1247-3p, hsa-miR-1247-3p, miR-1268a, hsa-miR-1268a, miR-1268b, hsa-miR-1268b, miR-1273g-3p, hsa-miR-1273g-3p, and miR-128-2-5p. -128-2-5p, miR-1343-3p is hsa-miR-1343-3p, miR-1343-5p is hsa-miR-1343-5p, miR-1470 is hsa-miR-1470, miR-17-3p is hsa-miR-17-3p, miR-187-5p is hsa-miR-187-5p, miR-1908-3p is hsa-miR-1908-3p, miR-1908-5p is hsa-miR-1908-5p, miR-1909-3p is hsa-miR-1909-3p, and m miR-1915-3p is hsa-miR-1915-3p, miR-210-5p is hsa-miR-210-5p, miR-24-3p is hsa-miR-24-3p, miR-2467-3p is hsa-miR-2467-3p, miR-2861 is hsa-miR-2861, miR-296-3p is hsa-miR-296-3p, miR-29b-3p is hsa-miR-29b-3p, miR-3131 is hsa-miR-3131, and miR-3154 is hsa-miR-3154;miR-3158-5p is hsa-miR-3158-5p, miR-3160-5p is hsa-miR-3160-5p, miR-3162-5p is hsa-miR-3162-5p, miR-3178 is hsa-miR-3178, miR-3180-3p is hsa-miR-3180-3p, and miR-3184-5p is hsa-miR-3 184-5p, miR-3185 is hsa-miR-3185, miR-3194-3p is hsa-miR-3194-3p, miR-3195 is hsa-miR-3195, miR-3197 is hsa-miR-3197, miR-320a is hsa-miR-320a, miR-320b is hsa-miR-320b, and miR- 328-5p is hsa-miR-328-5p, miR-342-5p is hsa-miR-342-5p, miR-345-3p is hsa-miR-345-3p, miR-3616-3p is hsa-miR-3616-3p, miR-3619-3p is hsa-miR-3619-3p, and miR-3620-5p is hsa-miR-3620- 5p, miR-3621 is hsa-miR-3621, miR-3622a-5p is hsa-miR-3622a-5p, miR-3648 is hsa-miR-3648, miR-3652 is hsa-miR-3652, miR-3656 is hsa-miR-3656, miR-3663-3p is hsa-miR-3663-3p, miR-3679-5p is hsa-miR-3679-5p, miR-371b-5p is hsa-miR-371b-5p, miR-373-5p is hsa-miR-373-5p, miR-3917 is hsa-miR-3917, miR-3940-5p is hsa-miR-3940-5p, miR-3960 is hsa-miR-3960, miR-4258 is hsa-miR-4258, miR-4259 is hsa-miR-4259, and miR-4270 is hsa-miR-4270. miR-4286 is hsa-miR-4286, miR-4298 is hsa-miR-4298, miR-4322 is hsa-miR-4322, miR-4327 is hsa-miR-4327, miR-4417 is hsa-miR-4417, miR-4419b is hsa-miR-4419b, miR-4429 is hsa-miR-4429, miR-4430 is hsa-miR-4430, miR-4433a-3p is hsa-miR-4433a-3p, and miR-44 36b-5p is hsa-miR-4436b-5p, miR-4443 is hsa-miR-4443, miR-4446-3p is hsa-miR-4446-3p, miR-4447 is hsa-miR-4447, miR-4448 is hsa-miR-4448, miR-4449 is hsa-miR-4449, miR-4454 is hsa-miR-4454, miR-4455 is hsa-miR-4455, miR-4459 is hsa-miR-4459, and miR-4462 is hsa-miR-4462. a-miR-4462, miR-4466 is hsa-miR-4466, miR-4467 is hsa-miR-4467, miR-4480 is hsa-miR-4480, miR-4483 is hsa-miR-4483, miR-4484 is hsa-miR-4484, miR-4485-5p is hsa-miR-4485-5p, miR-4488 is hsa-miR-4488, miR-4492 is hsa-miR-4492, and miR-4505 is hsa-miR-4505;miR-4515 is hsa-miR-4515, miR-4525 is hsa-miR-4525, miR-4534 is hsa-miR-4534, miR-4535 is hsa-miR-4535, miR-4633-3p is hsa-miR-4633-3p, miR-4634 is hsa-miR-4634, miR-4640-5p is hsa-miR-4640-5p, miR-4649-5p is hsa-miR-4649-5p, miR-4651 is hsa-miR-4651, and miR- 4652-5p is hsa-miR-4652-5p, miR-4655-5p is hsa-miR-4655-5p, miR-4656 is hsa-miR-4656, miR-4658 is hsa-miR-4658, miR-4663 is hsa-miR-4663, miR-4673 is hsa-miR-4673, miR-4675 is hsa-miR-4675, miR-4687-3p is hsa-miR-4687-3p, miR-4687-5p is hsa-miR-4687-5p, and mi miR-4690-5p is hsa-miR-4690-5p, miR-4695-5p is hsa-miR-4695-5p, miR-4697-5p is hsa-miR-4697-5p, miR-4706 is hsa-miR-4706, miR-4707-3p is hsa-miR-4707-3p, miR-4707-5p is hsa-miR-4707-5p, miR-4708-3p is hsa-miR-4708-3p, miR-4710 is hsa-miR-4710, and miR-4718 is hsa- miR-4718, miR-4722-5p is hsa-miR-4722-5p, miR-4725-3p is hsa-miR-4725-3p, miR-4726-5p is hsa-miR-4726-5p, miR-4727-3p is hsa-miR-4727-3p, miR-4728-5p is hsa-miR-4728-5p, miR-4731-5p is hsa-miR-4731-5p, miR-4736 is hsa-miR-4736, and miR-4739 is hsa-miR-4739;miR-4740-5p is hsa-miR-4740-5p, miR-4741 is hsa-miR-4741, miR-4750-5p is hsa-miR-4750-5p, miR-4755-3p is hsa-miR-4755-3p, miR-4763-3p is hsa-miR-4763-3p, miR-4771 is hsa-miR-4771, miR-4783-3p is hsa-miR-4783-3p, miR-4783-5p is hsa-miR-4783-5p, and miR-4787-3p hsa-miR-4787-3p, miR-4792 is hsa-miR-4792, miR-498 is hsa-miR-498, miR-5008-5p is hsa-miR-5008-5p, miR-5010-5p is hsa-miR-5010-5p, miR-504-3p is hsa-miR-504-3p, miR-5195-3p is hsa-miR-5195-3p, miR-550a-5p is hsa-miR-550a-5p, miR-5572 is hsa-miR-5572, and miR -5739 is hsa-miR-5739, miR-6075 is hsa-miR-6075, miR-6076 is hsa-miR-6076, miR-6088 is hsa-miR-6088, miR-6124 is hsa-miR-6124, miR-6131 is hsa-miR-6131, miR-6132 is hsa-miR-6132, miR-614 is hsa-miR-614, miR-615-5p is hsa-miR-615-5p, and miR-619-5p is hsa-miR-619-5 p, miR-642b-3p is hsa-miR-642b-3p, miR-6510-5p is hsa-miR-6510-5p, miR-6511a-5p is hsa-miR-6511a-5p, miR-6515-3p is hsa-miR-6515-3p, miR-6515-5p is hsa-miR-6515-5p, miR-663b is hsa-miR-663b, miR-6716-5p is hsa-miR-6716-5p, miR-6717-5p is hsa-miR-6717-5p,miR-6722-3p is hsa-miR-6722-3p, miR-6724-5p is hsa-miR-6724-5p, miR-6726-5p is hsa-miR-6726-5p, miR-6737-5p is hsa-miR-6737-5p, miR-6741-5p is hsa-miR-6741-5p, miR-6742-5p is hsa-miR-6742-5p, miR-6743-5p is hsa-miR-6743-5p, miR-6746-5p is hsa-miR-6746-5p, miR-6749-5p is hsa-miR-6749-5p, miR-6760-5p is hsa-miR-6760-5p, miR-6762-5p is hsa-miR-6762-5p, miR-6765-3p is hsa-miR-6765-3p, miR-6765-5p is hsa-miR-6765-5p, miR-6766-3p is hsa-miR-6766-3p, miR-6766-5p is hsa-miR-6766-5p, miR-6771-5p is hsa-miR-6771-5p, and m miR-6774-5p is hsa-miR-6774-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6778-5p is hsa-miR-6778-5p, miR-6780b-5p is hsa-miR-6780b-5p, miR-6781-5p is hsa-miR-6781-5p, miR-6782-5p is hsa-miR-6782-5p, miR-6784-5p is hsa-miR-6784-5p, and miR-6785-5p is hsa-miR-6785-5p. , miR-6787-5p is hsa-miR-6787-5p, miR-6789-5p is hsa-miR-6789-5p, miR-6791-5p is hsa-miR-6791-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6800-5p is hsa-miR-6800-5p, miR-6802-5p is hsa-miR-6802-5p, miR-6803-5p is hsa-miR-6803-5p, miR-6812-5p is hsa-miR-6812-5p,miR-6816-5p is hsa-miR-6816-5p, miR-6819-5p is hsa-miR-6819-5p, miR-6821-5p is hsa-miR-6821-5p, miR-6826-5p is hsa-miR-6826-5p, miR-6831-5p is hsa-miR-6831-5p, miR-6836-3p is hsa-miR-6836-3p, miR-6840-3p is hsa-miR-6840-3p, and miR-6 miR-6842-5p is hsa-miR-6842-5p, miR-6850-5p is hsa-miR-6850-5p, miR-6861-5p is hsa-miR-6861-5p, miR-6869-5p is hsa-miR-6869-5p, miR-6870-5p is hsa-miR-6870-5p, miR-6877-5p is hsa-miR-6877-5p, miR-6879-5p is hsa-miR-6879-5p, and miR-6880-3p is hsa-miR-6880-3p , miR-6880-5p is hsa-miR-6880-5p, miR-6885-5p is hsa-miR-6885-5p, miR-6887-5p is hsa-miR-6887-5p, miR-7107-5p is hsa-miR-7107-5p, miR-7108-3p is hsa-miR-7108-3p, miR-7109-5p is hsa-miR-7109-5p, miR-711 is hsa-miR-711, and miR-7113-3p is hsa-miR-7113-3p , miR-7150 is hsa-miR-7150, miR-744-5p is hsa-miR-744-5p, miR-7975 is hsa-miR-7975, miR-7977 is hsa-miR-7977, miR-8052 is hsa-miR-8052, miR-8069 is hsa-miR-8069, miR-8073 is hsa-miR-8073, miR-887-3p is hsa-miR-887-3p, and miR-937-5p is hsa-miR-937-5p.
[0609] In one embodiment, the nucleic acid (specifically, the probe or primer) in the method of the present invention is a polynucleotide shown in any one of the following (a) to (e): (a) a polynucleotide consisting of a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228 or a nucleotide sequence in which u is t in the nucleotide sequence, a mutant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive nucleotides; (b) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 1 to 228; (c) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence complementary to the base sequence in which u is t, or a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 1 to 228 or a base sequence in which u is t in the base sequence; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); is selected from the group consisting of:
[0610] In the method of the present invention, the expression level of at least one polynucleotide selected from miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940 can also be measured.
[0611] Specifically, miR-1202 is hsa-miR-1202, miR-1207-5p is hsa-miR-1207-5p, miR-1246 is hsa-miR-1246, miR-1254 is hsa-miR-1254, miR-135a-3p is hsa-miR-135a-3p, miR-1469 is hsa-miR-1469, miR-149-3p is hsa-miR-149-3p, and miR-150-3p is hsa- miR-150-3p, miR-1914-3p is hsa-miR-1914-3p, miR-191-5p is hsa-miR-191-5p, miR-423-5p is hsa-miR-423-5p, miR-663a is hsa-miR-663a, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-92a-3p is hsa-miR-92a-3p, and miR-940 is hsa-miR-940.
[0612] Furthermore, in one embodiment, the expression level of the polynucleotide is measured using a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is any one of the following polynucleotides (f) to (j): (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 229 to 243 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 comprising a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243; (h) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any one of SEQ ID NOs: 229 to 243 or the nucleotide sequence in which u is t, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive nucleotides; (i) a polynucleotide comprising a base sequence complementary to a base sequence represented by any one of SEQ ID NOs: 229 to 243 or a base sequence in which u is t in the base sequence; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); is selected from the group consisting of:
[0613] Examples of specimens used in the methods of the present invention include specimens prepared from a subject's biological tissue (preferably bladder tissue or renal pelvis or ureter tissue), and body fluids such as blood, serum, plasma, and urine.Specific examples include RNA-containing specimens prepared from the tissue, polynucleotide-containing specimens further prepared from the tissue, body fluids such as blood, serum, plasma, and urine, and biological tissues obtained by biopsy or the like, or by surgical removal of part or all of the subject's biological tissue, from which specimens for measurement can be prepared.
[0614] As used herein, a subject refers to a mammal, such as, but not limited to, a human, a monkey, a mouse, a rat, etc., and is preferably a human.
[0615] The steps of the method of the present invention can be changed depending on the type of specimen to be measured.
[0616] When RNA is used as the measurement target, a method for detecting bladder cancer (cells) includes, for example, the following steps (a), (b), and (c): (a) binding RNA prepared from a specimen of a subject (wherein, for the quantitative RT-PCR in step (b), for example, the 3' end of the RNA may be polyadenylated, or any sequence may be added to either or both ends by a ligation method or the like) or a complementary polynucleotide (cDNA) transcribed therefrom to a polynucleotide of the kit of the present invention; (b) measuring the sample-derived RNA or cDNA synthesized from the RNA bound to the polynucleotide by hybridization using the polynucleotide as a nucleic acid probe or by quantitative RT-PCR using the polynucleotide as a primer; (c) assessing the presence or absence of bladder cancer (or a gene derived from bladder cancer) based on the measurement results of (b) above; may include:
[0617] To measure the expression level of a target gene according to the present invention, various hybridization methods can be used, for example. Examples of such hybridization methods include Northern blotting, Southern blotting, DNA chip analysis, in situ hybridization, Northern hybridization, and Southern hybridization. PCR methods such as quantitative RT-PCR or next-generation sequencing can also be used in combination with or as an alternative to hybridization methods.
[0618] When using the Northern blot method, for example, the presence or absence of expression of each gene in RNA and the expression level thereof can be detected and measured by using the above-mentioned nucleic acid probes that can be used in the present invention. Specifically, the nucleic acid probe (complementary strand) can be ionized with a radioisotope ( 32 P, 33 P, 35 An example of such a method is to label the DNA / RNA with a radioisotope or fluorescent substance, and then hybridize it with RNA derived from the subject's biological tissue that has been transferred to a nylon membrane or the like in a standard manner. Then, the signal derived from the label (radioisotope or fluorescent substance) of the formed DNA / RNA double strand is detected and measured using a radiation detector (e.g., BAS-1800II (Fujifilm Corporation)) or a fluorescence detector (e.g., STORM 865 (GE Healthcare)).
[0619] When quantitative RT-PCR is used, the presence or absence of gene expression in RNA and its expression level can be detected and measured, for example, by using the primers usable in the present invention. For example, RNA is collected from a subject's biological tissue, the 3' end is polyadenylated, and cDNA is prepared from the polyadenylated RNA according to standard methods. Using this as a template, a pair of primers (consisting of a forward strand and a reverse strand that bind to the cDNA) that can be included in the detection kit or device of the present invention are hybridized to the cDNA, allowing amplification of the region of each target gene marker. PCR is then performed according to standard methods, and the resulting single-stranded or double-stranded DNA is detected. Examples of methods for detecting single-stranded or double-stranded DNA include PCR using primers that have been pre-labeled with radioisotopes or fluorescent substances; electrophoresis of PCR products on agarose gels followed by staining and detecting double-stranded DNA with ethidium bromide or the like; and transfer of the resulting single-stranded or double-stranded DNA to a nylon membrane or the like according to standard methods, followed by hybridization with a labeled nucleic acid probe for detection.
[0620] When nucleic acid array analysis is used, for example, an RNA chip or DNA chip is used in which the above-mentioned detection kit or device of the present invention is attached to a substrate (solid phase) as a nu...
Claims
1. A kit for detecting bladder cancer, comprising a nucleic acid, The kit comprises a nucleic acid probe capable of specifically binding to a polynucleotide of miR-6088, a bladder cancer marker, and / or a primer for specifically recognizing and amplifying the polynucleotide.
2. The nucleic acid is a polynucleotide represented by any one of (a) to (e) below: (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (b) a polynucleotide comprising the base sequence represented by SEQ ID NO: 150; (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The kit of claim 1, wherein the polynucleotide is selected from the group consisting of:
3. The kit includes miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, which are another bladder cancer marker.miR-4505、miR-4515、miR-4525、miR-4534、miR-4535、miR-4633-3p、miR-4 634、miR-4640-5p、miR-4649-5p、miR-4651、miR-4655-5p、miR-4656、miR- 4658、miR-4663、miR-4673、miR-4675、miR-4687-3p、miR-4687-5p、miR-46 90-5p、miR-4695-5p、miR-4697-5p、miR-4706、miR-4707-3p、miR-4707-5p、 miR-4708-3p、miR-4710、miR-4718、miR-4722-5p、miR-4725-3p、miR-4726 -5p、miR-4727-3p、miR-4728-5p、miR-4731-5p、miR-4736、miR-4739、miR-4 740-5p、miR-4741、miR-4750-5p、miR-4755-3p、miR-4763-3p、miR-4771、m iR-4783-3p、miR-4783-5p、miR-4787-3p、miR-4792、miR-498、miR-5008-5p 、miR-5010-5p、miR-504-3p、miR-5195-3p、miR-550a-5p、miR-5572、miR-5 739、miR-6075、miR-6076、miR-61124、miR-61131、miR-61132、miR-6114、miR-611 5-5p、miR-619-5p、miR-642b-3p、miR-6510-5p、miR-6511a-5p、miR-6515- 3p、miR-6515-5p、miR-663b、miR-6716-5p、miR-6717-5p、miR-6722-3p、miR -6724-5p、miR-6726-5p、miR-6737-5p、miR-6741-5p、miR-6742-5p、miR-6 743-5p、miR-6746-5p、miR-6749-5p、miR-6760-5p、miR-6762-5p、miR-6765 -3p、miR-6765-5p、miR-6766-3p、miR-6766-5p、miR-6771-5p、miR-6774-5 p、miR-6777-5p、miR-6778-5p、miR-6780b-5p、miR-6781-5p、miR-6782-5p、miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, mi R-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR- 6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-68 80-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, m iR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, miR-1202, miR -1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR-42 The kit according to claim 1 or 2, further comprising an additional nucleic acid comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from miR-6087, miR-3-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940 (excluding a combination of polynucleotides comprising miR-6087 and miR-1185-1-3p) and / or a primer for specifically recognizing and amplifying the polynucleotide.
4. The additional nucleic acid is a polynucleotide shown in any one of (f) to (j) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence; or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243; (h) a polynucleotide consisting of a base sequence complementary to any of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity with the base sequence; or a fragment thereof containing 15 or more consecutive bases; (i) a polynucleotide comprising a base sequence complementary to any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or the base sequence in which u is t; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The kit of claim 3, wherein the polynucleotide is selected from the group consisting of:
5. A device for detecting bladder cancer, comprising a nucleic acid, The device, wherein the nucleic acid comprises a nucleic acid probe capable of specifically binding to a polynucleotide of miR-6088, a bladder cancer marker, and / or a primer for specifically recognizing and amplifying the polynucleotide.
6. The nucleic acid is a polynucleotide represented by any one of (a) to (e) below: (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (b) a polynucleotide comprising the base sequence represented by SEQ ID NO: 150; (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The device of claim 5, wherein the polynucleotide is selected from the group consisting of:
7. The device is another bladder cancer marker, miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-394-.-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492miR-4505、miR-4515、miR-4525、miR-4534、miR-4535、miR-4633-3p、miR-4 634、miR-4640-5p、miR-4649-5p、miR-4651、miR-4655-5p、miR-4656、miR- 4658、miR-4663、miR-4673、miR-4675、miR-4687-3p、miR-4687-5p、miR-46 90-5p、miR-4695-5p、miR-4697-5p、miR-4706、miR-4707-3p、miR-4707-5p、 miR-4708-3p、miR-4710、miR-4718、miR-4722-5p、miR-4725-3p、miR-4726 -5p、miR-4727-3p、miR-4728-5p、miR-4731-5p、miR-4736、miR-4739、miR-4 740-5p、miR-4741、miR-4750-5p、miR-4755-3p、miR-4763-3p、miR-4771、m iR-4783-3p、miR-4783-5p、miR-4787-3p、miR-4792、miR-498、miR-5008-5p 、miR-5010-5p、miR-504-3p、miR-5195-3p、miR-550a-5p、miR-5572、miR-5 739、miR-6075、miR-6076、miR-61124、miR-61131、miR-61132、miR-6114、miR-611 5-5p、miR-619-5p、miR-642b-3p、miR-6510-5p、miR-6511a-5p、miR-6515- 3p、miR-6515-5p、miR-663b、miR-6716-5p、miR-6717-5p、miR-6722-3p、miR -6724-5p、miR-6726-5p、miR-6737-5p、miR-6741-5p、miR-6742-5p、miR-6 743-5p、miR-6746-5p、miR-6749-5p、miR-6760-5p、miR-6762-5p、miR-6765 -3p、miR-6765-5p、miR-6766-3p、miR-6766-5p、miR-6771-5p、miR-6774-5 p、miR-6777-5p、miR-6778-5p、miR-6780b-5p、miR-6781-5p、miR-6782-5p、miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802-5p, mi R-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-6836-3p, miR- 6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR-6879-5p, miR-68 80-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887-3p, miR-937-5p, miR-1202, mi R-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150-3p, miR-1914-3p, miR-191-5p, miR- The device according to claim 5 or 6, further comprising an additional nucleic acid comprising a nucleic acid probe capable of specifically binding to at least one polynucleotide selected from miR-6087, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940 (excluding a combination of polynucleotides comprising miR-6087 and miR-1185-1-3p) and / or a primer for specifically recognizing and amplifying the polynucleotide.
8. The additional nucleic acid is a polynucleotide shown in any one of (f) to (j) below: (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence; or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243; (h) a polynucleotide consisting of a base sequence complementary to any of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity with the base sequence; or a fragment thereof containing 15 or more consecutive bases; (i) a polynucleotide comprising a base sequence complementary to any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or the base sequence in which u is t; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The device of claim 7, wherein the polynucleotide is selected from the group consisting of:
9. The device according to any one of claims 5 to 8, which is a device for measurement by hybridization technology.
10. The device of claim 9 , wherein the hybridization technology is a nucleic acid array technology.
11. measuring in vitro the expression level of a polynucleotide of miR-6088, a bladder cancer marker, in a specimen from the subject of interest, wherein the measured expression level is used to assist in assessing whether the subject is affected with bladder cancer; The aiding in the evaluation includes substituting the measured expression levels into a discriminant that is created based on discriminant analysis using the gene expression levels of a specimen derived from a subject known to have bladder cancer and the gene expression levels of a specimen derived from a subject not affected with bladder cancer as teacher samples, and that is capable of discriminating between the presence or absence of bladder cancer, and using the obtained discriminant score to aid in the evaluation of the presence or absence of bladder cancer. A method to aid in the detection of bladder cancer.
12. The expression level of the polynucleotide is measured using a nucleic acid probe capable of specifically binding to the polynucleotide and / or a nucleic acid containing a primer for specifically recognizing and amplifying the polynucleotide, and the nucleic acid is determined to be a polynucleotide selected from any of the following (a) to (e): (a) a polynucleotide consisting of the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (b) a polynucleotide comprising the base sequence represented by SEQ ID NO: 150; (c) a polynucleotide consisting of a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t, a polynucleotide consisting of a base sequence having 90% or more identity to the base sequence, or a fragment thereof containing 15 or more consecutive bases; (d) a polynucleotide comprising a base sequence complementary to the base sequence represented by SEQ ID NO: 150 or the base sequence in which u is t; and (e) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (a) to (d); The method of claim 11, wherein the polynucleotide is selected from the group consisting of:
13. Another bladder cancer marker, miR-6087, miR-1185-1-3p, miR-1185-2-3p, miR-1193, miR-1199-5p, miR-1225-5p, miR-1227-5p, miR-1228-3p, miR-1228-5p, miR-1237-5p, miR-1238-5p, miR-1247-3p, miR-1268a, miR-1268b, miR-1273g-3p, miR-128-2-5p, miR-1343-3p, miR-1343-5p, miR-1470, miR-17-3p, miR-187-5p, miR-1908-3p, miR-1908-5p, miR-1909-3p, miR-1915-3p, miR-210-5p, miR-24-3p, miR-2467-3p, miR-2861, miR-296-3p, miR-29b-3p, miR-3131, miR-3154, miR-3158-5p, miR-3160-5p, miR-3162-5p, miR-3178, miR-3180-3p, miR-3184-5p, miR-3185, miR-3194-3p, miR-3195, miR-3197, miR-320a, miR-320b, miR-328-5p, miR-342-5p, miR-345-3p, miR-3616-3p, miR-3619-3p, miR-3620-5p, miR-3621, miR-3622a-5p, miR-3648, miR-3652, miR-3656, miR-3663-3p, miR-3679-5p, miR-371b-5p, miR-373-5p, miR-3917, miR-3940-5p, miR-3960, miR-4258, miR-4259, miR-4270, miR-4286, miR-4298, miR-4322, miR-4327, miR-4417, miR-4419b, miR-4429, miR-4430, miR-4433a-3p, miR-4436b-5p, miR-�4443, miR-4446-3p, miR-4447, miR-4448, miR-4449, miR-4454, miR-4455, miR-4459, miR-4462, miR-4466, miR-4467, miR-4480, miR-4483, miR-4484, miR-4485-5p, miR-4488, miR-4492, miR-4505miR-45115、miR-4525、miR-4534、miR-4535、miR-4633-3p、miR-4634、miR- 4640-5p、miR-4649-5p、miR-4651、miR-4655-5p、miR-4656、miR-4656、miR-4658、miR -4663、miR-4673、miR-4675、miR-4687-3p、miR-4687-5p、miR-4690-5p、mi R-4695-5p、miR-4697-5p、miR-4706、miR-4707-3p、miR-4707-5p、miR-470 8-3p、miR-4710、miR-4718、miR-4722-5p、miR-4725-3p、miR-4726-5p、miR -4727-3p、miR-4728-5p、miR-4731-5p、miR-4736、miR-4739、miR-4740-5p 、miR-4741、miR-4750-5p、miR-4755-3p、miR-4763-3p、miR-4771、miR-478 3-3p、miR-4783-5p、miR-4787-3p、miR-4792、miR-498、miR-5008-5p、miR- 5010-5p、miR-504-3p、miR-5195-3p、miR-550a-5p、miR-5572、miR-5739、 miR-6075、miR-6076、miR-6124、miR-6131、miR-6132、miR-614、miR-615-5 p、miR-619-5p、miR-642b-3p、miR-6510-5p、miR-6511a-5p、miR-6515-3p、 miR-6515-5p、miR-663b、miR-6716-5p、miR-6717-5p、miR-6722-3p、miR-6 724-5p、miR-6726-5p、miR-6737-5p、miR-6741-5p、miR-6742-5p、miR-674 3-5p、miR-6746-5p、miR-6749-5p、miR-6760-5p、miR-6762-5p、miR-6765- 3p、miR-6765-5p、miR-6766-3p、miR-6766-5p、miR-6771-5p、miR-6774-5p 、miR-6777-5p、miR-6778-5p、miR-6780b-5p、miR-6781-5p、miR-6782-5p、miR-6784-5p, miR-6785-5p, miR-6787-5p, miR-6789-5p, miR-6791-5p, miR-6794-5p, miR-6800-5p, miR-6802- 5p, miR-6803-5p, miR-6812-5p, miR-6816-5p, miR-6819-5p, miR-6821-5p, miR-6826-5p, miR-6831-5p, miR-68 36-3p, miR-6840-3p, miR-6842-5p, miR-6850-5p, miR-6861-5p, miR-6869-5p, miR-6870-5p, miR-6877-5p, miR -6879-5p, miR-6880-3p, miR-6880-5p, miR-6885-5p, miR-6887-5p, miR-7107-5p, miR-7108-3p, miR-7109-5p, miR-711, miR-7113-3p, miR-7150, miR-744-5p, miR-7975, miR-7977, miR-8052, miR-8069, miR-8073, miR-887- 3p, miR-937-5p, miR-1202, miR-1207-5p, miR-1246, miR-1254, miR-135a-3p, miR-1469, miR-149-3p, miR-150- The method according to claim 11 or 12, further comprising measuring the expression level of at least one additional polynucleotide selected from miR-6087, miR-6087-2, miR-92a-3p, miR-1914-3p, miR-191-5p, miR-423-5p, miR-663a, miR-92a-2-5p, miR-92a-3p, and miR-940 (excluding a combination of polynucleotides including miR-6087 and miR-1185-1-3p).
14. The expression level of the additional polynucleotide is measured using an additional nucleic acid comprising a nucleic acid probe capable of specifically binding to the additional polynucleotide and / or a primer for specifically recognizing and amplifying the polynucleotide, and the additional nucleic acid is a polynucleotide selected from any of the following (f) to (j): (f) a polynucleotide consisting of a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity to the base sequence; or a fragment thereof containing 15 or more consecutive bases; (g) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243; (h) a polynucleotide consisting of a base sequence complementary to any of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or a base sequence in which u is t in the base sequence; a polynucleotide consisting of a base sequence having 90% or more percent identity with the base sequence; or a fragment thereof containing 15 or more consecutive bases; (i) a polynucleotide comprising a base sequence complementary to any one of SEQ ID NOs: 1 to 103, 105 to 149, and 151 to 243, or the base sequence in which u is t; and (j) a polynucleotide that hybridizes under stringent conditions with any one of the polynucleotides (f) to (i); The method of claim 13, wherein the polynucleotide is selected from the group consisting of:
15. The method according to any one of claims 11 to 14, wherein the expression level of a target gene in a specimen from a subject is measured in vitro using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10, which comprises a nucleic acid comprising a nucleic acid probe capable of specifically binding to the polynucleotide and / or a primer for specifically recognizing and amplifying the polynucleotide.
16. The method of any one of claims 11 to 15, wherein the subject is a human.
17. The method according to any one of claims 11 to 16, wherein the sample is blood, serum, or plasma.
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