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CA-3296926-A1 - LIVER CANCER DETECTION KIT OR DEVICE, AND DETECTION METHOD

CA3296926A1CA 3296926 A1CA3296926 A1CA 3296926A1CA-3296926-A1

Abstract

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

Inventors

  • Satoshi Kondou
  • Hitoshi Nobumasa
  • Satoko Kozono
  • Hiroko SUDO
  • Junpei KAWAUCHI
  • Atsushi Ochiai
  • Motohiro Kojima

Assignees

  • TORAY INDUSTRIES, INC.
  • NATIONAL CANCER CENTER

Dates

Publication Date
20260302
Application Date
20150618
Priority Date
20140618

Claims (16)

  1. <pat:ClaimStatement>1. A kit for use in the detection of liver cancer, wherein said kit comprises one or more nucleic acids capable of specifically binding to a polynucleotide of liver cancer marker miR-6724-5p, and instructions for using said kit in the detection of liver cancer.
  2. 2. The kit for use according to claim 1, wherein the one or more nucleic acids are one or more polynucleotides selected from the group consisting of the following polynucleotides (a)(1) to (a)(5), (b), <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>c</mi><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mn>6</mn><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(c)(6)</annotation></semantics></math> to <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>c</mi><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mn>10</mn><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(c)(10)</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>d</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(d)</annotation></semantics></math> and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>e</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(e)</annotation></semantics></math>: (a) (1) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t,</pat:ClaimStatement> <pat:Claims com:id="claims"> <pat:Claim com:id="CLM-00002"> <pat:ClaimNumber>2</pat:ClaimNumber> <pat:ClaimText>2. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (1), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00003"> <pat:ClaimNumber>3</pat:ClaimNumber> <pat:ClaimText>3. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (1) or (2), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00004"> <pat:ClaimNumber>4</pat:ClaimNumber> <pat:ClaimText>4. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (1) or (2), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00005"> <pat:ClaimNumber>5</pat:ClaimNumber> <pat:ClaimText>5. a polynucleotide of any one of (1) to (4) which contains a modified nucleic acid or a modified nucleotide, (b) a polynucleotide comprising a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, (c) (6) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00007"> <pat:ClaimNumber>7</pat:ClaimNumber> <pat:ClaimText>7. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (6), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00008"> <pat:ClaimNumber>8</pat:ClaimNumber> <pat:ClaimText>8. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (6) or (7), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00009"> <pat:ClaimNumber>9</pat:ClaimNumber> <pat:ClaimText>9. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (6) or (7), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00010"> <pat:ClaimNumber>10</pat:ClaimNumber> <pat:ClaimText>10. a polynucleotide of any one of (6) to (9) which contains a modified nucleic acid or a modified nucleotide, (d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, and (e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d), wherein the stringent conditions comprise hybridization conditions: 30°C to 60°C for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate and a blocking agent; and washing conditions: following the hybridization, continuous washing at 30°C in a solution containing 0.5% SSC and 0.1% SDS, at 30°C in a solution containing 0.2% SSC and 0.1% SDS, and at 30°C in a 0.05% SSC solution.
  3. 3. The kit for use according to claim 1 or 2, wherein the kit further comprises one or more nucleic acids capable of specifically binding to one or more polynucleotides selected from the group consisting of other liver cancer markers: miR-1343-3p, miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR- 3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p, miR-6717-5p, miR- 6870-5p, miR-663b, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR- 4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR-296-5p, miR- 3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR-6872-3p, miR- 4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632- 5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p, miR- 5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826- 5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649-5p, miR-4525, miR-1915-3p, miR- 4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p, miR-4739, miR-4459, miR- 1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343-5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR-939- 5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774- 5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508, miR-6806-5p, miR- 7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6757-5p, miR- 4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR- 4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and miR-6836-3p, and/or; miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187- 5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p, miR- 663a, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR- 3180, miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR- 4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557, and miR-6090.
  4. 4. The kit for use according to claim 3, wherein the one or more nucleic acids are either or both of I) or II) as follows: I) one or more polynucleotides selected from the group consisting of the following polynucleotides (a)'(11) to (a)'(15), (b)', (c)'(16) to (c)'(20), (d)' and (e)': (a)' (11) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00012"> <pat:ClaimNumber>12</pat:ClaimNumber> <pat:ClaimText>12. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (11), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00013"> <pat:ClaimNumber>13</pat:ClaimNumber> <pat:ClaimText>13. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (11) or (12), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00014"> <pat:ClaimNumber>14</pat:ClaimNumber> <pat:ClaimText>14. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (11) or (12), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00015"> <pat:ClaimNumber>15</pat:ClaimNumber> <pat:ClaimText>15. a polynucleotide of any one of (11) to (14) which contains a modified nucleic acid or a modified nucleotide, (b)' a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, (c)' (16) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00017"> <pat:ClaimNumber>17</pat:ClaimNumber> <pat:ClaimText>17. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (16), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00018"> <pat:ClaimNumber>18</pat:ClaimNumber> <pat:ClaimText>18. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (16) or (17), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00019"> <pat:ClaimNumber>19</pat:ClaimNumber> <pat:ClaimText>19. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (16) or (17), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00020"> <pat:ClaimNumber>20</pat:ClaimNumber> <pat:ClaimText>20. a polynucleotide of any one of (16) to (19) which contains a modified nucleic acid or a modified nucleotide, (d)' a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, and (e)' a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a)' to (d)'; II) one or more polynucleotides selected from the group consisting of the following polynucleotides (f)(21) to (f)(25), (g), (h)(26) to (h)(30), (i), (j), (k)(31) to (k)(35), (l), (m)(36) to <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>m</mi><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mn>40</mn><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(m)(40)</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>n</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(n)</annotation></semantics></math> and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>o</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(o)</annotation></semantics></math>: (f) (21) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00022"> <pat:ClaimNumber>22</pat:ClaimNumber> <pat:ClaimText>22. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (21), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00023"> <pat:ClaimNumber>23</pat:ClaimNumber> <pat:ClaimText>23. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (21) or (22), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00024"> <pat:ClaimNumber>24</pat:ClaimNumber> <pat:ClaimText>24. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (21) or (22), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00025"> <pat:ClaimNumber>25</pat:ClaimNumber> <pat:ClaimText>25. a polynucleotide of any one of (21) to (24) which contains a modified nucleic acid or a modified nucleotide, (g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, (h) (26) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00027"> <pat:ClaimNumber>27</pat:ClaimNumber> <pat:ClaimText>27. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (26), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00028"> <pat:ClaimNumber>28</pat:ClaimNumber> <pat:ClaimText>28. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (26) or (27), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00029"> <pat:ClaimNumber>29</pat:ClaimNumber> <pat:ClaimText>29. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (26) or (27), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00030"> <pat:ClaimNumber>30</pat:ClaimNumber> <pat:ClaimText>30. a polynucleotide of any one of (26) to (29) which contains a modified nucleic acid or a modified nucleotide, (i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, (j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>f</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(f)</annotation></semantics></math> to <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>i</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(i)</annotation></semantics></math>, (k) (31) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00032"> <pat:ClaimNumber>32</pat:ClaimNumber> <pat:ClaimText>32. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (31), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00033"> <pat:ClaimNumber>33</pat:ClaimNumber> <pat:ClaimText>33. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (31) or (32), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00034"> <pat:ClaimNumber>34</pat:ClaimNumber> <pat:ClaimText>34. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (31) or (32), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00035"> <pat:ClaimNumber>35</pat:ClaimNumber> <pat:ClaimText>35. a polynucleotide of any one of (31) to (34) which contains a modified nucleic acid or a modified nucleotide, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00001"> <pat:ClaimNumber>1</pat:ClaimNumber> <pat:ClaimText>1. a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, (m) (36) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00037"> <pat:ClaimNumber>37</pat:ClaimNumber> <pat:ClaimText>37. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (36), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00038"> <pat:ClaimNumber>38</pat:ClaimNumber> <pat:ClaimText>38. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (36) or (37), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00039"> <pat:ClaimNumber>39</pat:ClaimNumber> <pat:ClaimText>39. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (36) or (37), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00040"> <pat:ClaimNumber>40</pat:ClaimNumber> <pat:ClaimText>40. a polynucleotide of any one of (36) to (39) which contains a modified nucleic acid or a modified nucleotide, (n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00000"> <pat:ClaimNumber>0</pat:ClaimNumber> <pat:ClaimText>0. a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n), wherein the stringent conditions comprise hybridization conditions: 30°C to 60°C for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate and a blocking agent; and washing conditions: following the hybridization, continuous washing at 30°C in a solution containing 0.5% SSC and 0.1% SDS, at 30°C in a solution containing 0.2% SSC and 0.1% SDS, and at 30°C in a 0.05% SSC solution.
  5. 5. A device for use in the detection of liver cancer, wherein said device comprises one or more nucleic acids capable of specifically binding to a polynucleotide of liver cancer marker miR-6724-5p, wherein said one or more nucleic acids are attached to a solid phase.
  6. 6. The device for use according to claim 5, wherein the one or more nucleic acids are one or more polynucleotides selected from the group consisting of the following polynucleotides (a)(41) to (a)(45), (b), <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>c</mi><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mn>46</mn><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(c)(46)</annotation></semantics></math> to <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>c</mi><mo stretchy="false" form="postfix">)</mo><mo stretchy="false" form="prefix">(</mo><mn>50</mn><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(c)(50)</annotation></semantics></math>, <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>d</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(d)</annotation></semantics></math> and <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>e</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(e)</annotation></semantics></math>: (a) (41) a polynucleotide consisting of a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00042"> <pat:ClaimNumber>42</pat:ClaimNumber> <pat:ClaimText>42. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (41), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00043"> <pat:ClaimNumber>43</pat:ClaimNumber> <pat:ClaimText>43. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (41) or (42), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00044"> <pat:ClaimNumber>44</pat:ClaimNumber> <pat:ClaimText>44. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (41) or (42), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00045"> <pat:ClaimNumber>45</pat:ClaimNumber> <pat:ClaimText>45. a polynucleotide of any one of (41) to (44) which contains a modified nucleic acid or a modified nucleotide, (b) a polynucleotide comprising a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, (c) (46) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00047"> <pat:ClaimNumber>47</pat:ClaimNumber> <pat:ClaimText>47. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (46), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00048"> <pat:ClaimNumber>48</pat:ClaimNumber> <pat:ClaimText>48. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (46) or (47), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00049"> <pat:ClaimNumber>49</pat:ClaimNumber> <pat:ClaimText>49. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (46) or (47), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00050"> <pat:ClaimNumber>50</pat:ClaimNumber> <pat:ClaimText>50. a polynucleotide of any one of (46) to (49) which contains a modified nucleic acid or a modified nucleotide, (d) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by SEQ ID NO: 167 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by SEQ ID NO: 167 by the replacement of u with t, and (e) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a) to (d), wherein the stringent conditions comprise hybridization conditions: 30°C to 60°C for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate and a blocking agent; and washing conditions: following the hybridization, continuous washing at 30°C in a solution containing 0.5% SSC and 0.1% SDS, at 30°C in a solution containing 0.2% SSC and 0.1% SDS, and at 30°C in a 0.05% SSC solution.
  7. 7. The device for use according to claim 5 or 6, wherein the device further comprises one or more nucleic acids capable of specifically binding to one or more polynucleotides selected from the group consisting of other liver cancer markers: miR-1343-3p, miR-6726-5p, miR-6515-3p, miR-4651, miR- 4257, miR-3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204-3p, miR-7977, miR-7110-5p, miR-6717- 5p, miR-6870-5p, miR-663b, miR-6875-5p, miR-8072, miR-6816-5p, miR-4281, miR-6729-5p, miR- 8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893-5p, miR-6857-5p, miR-1227-5p, miR- 6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR- 1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR- 296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR- 4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887-5p, miR-6738-5p, miR- 6872-3p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914- 3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR- 1228-5p, miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR-6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891- 5p, miR-6826-5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649-5p, miR-4525, miR- 1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848-5p, miR-4739, miR- 4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR-6510-5p, miR-1343- 5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858-5p, miR-3937, miR- 939-5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR-3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774- 5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR-4508, miR-6806-5p, miR- 7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752-5p, miR-6757-5p, miR- 4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR-4484, miR-4634, miR- 4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and miR-6836-3p, and/or; miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187- 5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b-5p, miR-92a-3p, miR- 663a, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR- 3180, miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR-6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR-6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR- 4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR-6089, miR-6124, miR-6778-5p, miR-557 and miR-6090.
  8. 8. The device for use according to claim 7, wherein the one or more nucleic acids are either or both of I) or II) as follows: I) one or more polynucleotides selected from the group consisting of the following polynucleotides (a)'(51) to (a)'(55), (b)', (c)'(56) to (c)'(60), (d)' and (e)': (a)' (51) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00052"> <pat:ClaimNumber>52</pat:ClaimNumber> <pat:ClaimText>52. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (51), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00053"> <pat:ClaimNumber>53</pat:ClaimNumber> <pat:ClaimText>53. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (51) or (52), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00054"> <pat:ClaimNumber>54</pat:ClaimNumber> <pat:ClaimText>54. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (51) or (52), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00055"> <pat:ClaimNumber>55</pat:ClaimNumber> <pat:ClaimText>55. a polynucleotide of any one of (51) to (54) which contains a modified nucleic acid or a modified nucleotide, (b)' a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, (c)' (56) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00057"> <pat:ClaimNumber>57</pat:ClaimNumber> <pat:ClaimText>57. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (56), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00058"> <pat:ClaimNumber>58</pat:ClaimNumber> <pat:ClaimText>58. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (56) or (57), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00059"> <pat:ClaimNumber>59</pat:ClaimNumber> <pat:ClaimText>59. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (56) or (57), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00060"> <pat:ClaimNumber>60</pat:ClaimNumber> <pat:ClaimText>60. a polynucleotide of any one of (56) to (59) which contains a modified nucleic acid or a modified nucleotide, (d)' a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 1 to 53, 55 to 166 and 714 to 729 by the replacement of u with t, and (e)' a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (a)' to (d)'; II) one or more polynucleotides selected from the group consisting of the following polynucleotides (f) to (f)(65), (g), (h)(66) to (h)(70), (i), (j), (k)(71) to (k)(75), (l), (m)(76) to (m)(80), (n) and (o): (f) (61) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00062"> <pat:ClaimNumber>62</pat:ClaimNumber> <pat:ClaimText>62. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (61), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00063"> <pat:ClaimNumber>63</pat:ClaimNumber> <pat:ClaimText>63. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (61) or (62), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00064"> <pat:ClaimNumber>64</pat:ClaimNumber> <pat:ClaimText>64. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (61) or (62), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00065"> <pat:ClaimNumber>65</pat:ClaimNumber> <pat:ClaimText>65. a polynucleotide of any one of (61) to (64) which contains a modified nucleic acid or a modified nucleotide, (g) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, (h) (66) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00067"> <pat:ClaimNumber>67</pat:ClaimNumber> <pat:ClaimText>67. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (66), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00068"> <pat:ClaimNumber>68</pat:ClaimNumber> <pat:ClaimText>68. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (66) or (77), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00069"> <pat:ClaimNumber>69</pat:ClaimNumber> <pat:ClaimText>69. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (66) or (67), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00070"> <pat:ClaimNumber>70</pat:ClaimNumber> <pat:ClaimText>70. a polynucleotide of any one of (66) to (69) which contains a modified nucleic acid or a modified nucleotide, (i) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 or a nucleotide sequence derived from the nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 168 to 183 by the replacement of u with t, (j) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>f</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(f)</annotation></semantics></math> to <math xmlns="http://www.w3.org/1998/Math/MathML"><semantics><mrow><mo stretchy="false" form="prefix">(</mo><mi>i</mi><mo stretchy="false" form="postfix">)</mo></mrow><annotation encoding="application/x-tex">(i)</annotation></semantics></math>, (k) (71) a polynucleotide consisting of a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00072"> <pat:ClaimNumber>72</pat:ClaimNumber> <pat:ClaimText>72. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (71), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00073"> <pat:ClaimNumber>73</pat:ClaimNumber> <pat:ClaimText>73. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (71) or (72), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00074"> <pat:ClaimNumber>74</pat:ClaimNumber> <pat:ClaimText>74. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (71) or (72), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00075"> <pat:ClaimNumber>75</pat:ClaimNumber> <pat:ClaimText>75. a polynucleotide of any one of (71) to (74) which contains a modified nucleic acid or a modified nucleotide, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00001"> <pat:ClaimNumber>1</pat:ClaimNumber> <pat:ClaimText>1. a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, (m) (76) a polynucleotide consisting of a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00077"> <pat:ClaimNumber>77</pat:ClaimNumber> <pat:ClaimText>77. a polynucleotide consisting of a fragment containing 15 or more consecutive nucleotides of the polynucleotide of (76), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00078"> <pat:ClaimNumber>78</pat:ClaimNumber> <pat:ClaimText>78. a polynucleotide containing a deletion, substitution, addition, or insertion of 1 or 2 nucleotides in the polynucleotide of (76) or (77), </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00079"> <pat:ClaimNumber>79</pat:ClaimNumber> <pat:ClaimText>79. a polynucleotide having a nucleotide sequence of 90% or higher identity to the nucleotide sequence of the polynucleotide of (76) or (77), and </pat:ClaimText> </pat:Claim> <pat:Claim com:id="CLM-00080"> <pat:ClaimNumber>80</pat:ClaimNumber> <pat:ClaimText>80. a polynucleotide of any one of (76) to (79) which contains a modified nucleic acid or a modified nucleotide, (n) a polynucleotide comprising a nucleotide sequence complementary to a nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 or a nucleotide sequence derived from the nucleotide sequence complementary to the nucleotide sequence represented by any of SEQ ID NOs: 184 to 224 by the replacement of u with t, and (o) a polynucleotide hybridizing under stringent conditions to any of the polynucleotides (k) to (n), wherein the stringent conditions comprise hybridization conditions: 30°C to 60°C for 1 to 24 hours in a solution containing SSC, a surfactant, formamide, dextran sulfate and a blocking agent; and washing conditions: following the hybridization, continuous washing at 30°C in a solution containing 0.5% SSC and 0.1% SDS, at 30°C in a solution containing 0.2% SSC and 0.1% SDS, and at 30°C in a 0.05% SSC solution.
  9. 9. The device for use according to any one of claims 5 to 8, wherein the device is a device for measurement by a hybridization technique.
  10. 10. The device for use according to claim 9, wherein the hybridization technique is a nucleic acid array technique.
  11. 11. A method for detecting liver cancer, comprising measuring an expression level of a target nucleic acid in a sample of a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10; and comparing the measured expression level with a control expression level for a healthy subject measured in the same way, and thereby determining whether or not the subject has liver cancer.
  12. 12. A method for detecting liver cancer, comprising measuring an expression level(s) of a target gene(s) in a sample from a subject using the kit according to any one of claims 1 to 4 or the device according to any one of claims 5 to 10; preparing a discriminant using, as training samples, expression levels of the gene(s) in samples from subjects known to have liver cancer and expression levels of the gene(s) in samples from healthy subjects and being capable of discriminating between the liver cancer and the healthy; assigning the expression level(s) of the target gene(s) in the sample from the subject to the discriminant; and determining whether or not the subject has liver cancer.
  13. 13. The method according to claim 11 or 12, wherein the subject is a human.
  14. 14. The method according to claim 11 or 12, wherein the sample is blood, serum, or plasma.
  15. 15. A marker for use in detection of liver cancer, comprising a polynucleotide of miR-6724-5p.
  16. 16. The marker for use in detection of liver cancer according to claim 15, wherein the marker further comprises one or more polynucleotides selected from the group consisting of: miR-1343-3p, miR-6726-5p, miR-6515-3p, miR-4651, miR-4257, miR-3188, miR-6131, miR-6766-3p, miR-7641, miR-1249, miR-3679-3p, miR-6787-5p, miR-4454, miR-3135b, miR-6765-3p, miR-7975, miR-204- 3p, miR-7977, miR-7110-5p, miR-6717-5p, miR-6870-5p, miR-663b, miR-6875-5p, miR-8072, miR- 6816-5p, miR-4281, miR-6729-5p, miR-8069, miR-4706, miR-7108-5p, miR-4433b-3p, miR-6893- 5p, miR-6857-5p, miR-1227-5p, miR-6741-5p, miR-451a, miR-8063, miR-3622a-5p, miR-615-5p, miR-128-1-5p, miR-6825-5p, miR-1260b, miR-4433-3p, miR-4665-5p, miR-7845-5p, miR-1908-5p, miR-6840-3p, miR-6765-5p, miR-296-5p, miR-3675-3p, miR-6781-5p, miR-423-5p, miR-3663-3p, miR-6749-5p, miR-1231, miR-4746-3p, miR-6780b-5p, miR-4758-5p, miR-3679-5p, miR-3184-5p, miR-6125, miR-6721-5p, miR-6791-5p, miR-3185, miR-1260a, miR-3197, miR-6845-5p, miR-6887- 5p, miR-6738-5p, miR-6872-3p, miR-4497, miR-1229-5p, miR-6820-5p, miR-6777-5p, miR-3917, miR-5787, miR-4286, miR-6877-5p, miR-1225-3p, miR-6088, miR-6800-5p, miR-1246, miR-4467, miR-4419b, miR-1914-3p, miR-4632-5p, miR-1915-5p, miR-3940-5p, miR-1185-2-3p, miR-6746-5p, miR-5001-5p, miR-1228-5p, miR-5572, miR-4327, miR-4638-5p, miR-6799-5p, miR-6861-5p, miR- 6727-5p, miR-4513, miR-6805-3p, miR-6808-5p, miR-4449, miR-1199-5p, miR-1275, miR-4792, miR-4443, miR-6891-5p, miR-6826-5p, miR-6807-5p, miR-7150, miR-4534, miR-4476, miR-4649- 5p, miR-4525, miR-1915-3p, miR-4516, miR-4417, miR-642b-3p, miR-3141, miR-5100, miR-6848- 5p, miR-4739, miR-4459, miR-1237-5p, miR-296-3p, miR-4665-3p, miR-6786-5p, miR-4258, miR- 6510-5p, miR-1343-5p, miR-1247-3p, miR-6805-5p, miR-4492, miR-1469, miR-1268b, miR-6858- 5p, miR-3937, miR-939-5p, miR-3656, miR-744-5p, miR-4687-3p, miR-4763-3p, miR-3620-5p, miR- 3195, miR-6842-5p, miR-4707-5p, miR-642a-3p, miR-7113-3p, miR-4728-5p, miR-5195-3p, miR-1185-1-3p, miR-6774-5p, miR-8059, miR-3131, miR-7847-3p, miR-4463, miR-128-2-5p, miR- 4508, miR-6806-5p, miR-7111-5p, miR-6782-5p, miR-4734, miR-3162-5p, miR-887-3p, miR-6752- 5p, miR-6757-5p, miR-4448, miR-671-5p, miR-3178, miR-4725-3p, miR-940, miR-6789-5p, miR- 4484, miR-4634, miR-4745-5p, miR-4730, miR-6803-5p, miR-6798-5p, miR-3648, miR-4783-3p and miR-6836-3p, and/or; miR-23b-3p, miR-23a-3p, miR-625-3p, miR-1228-3p, miR-614, miR-1913, miR-92a-2-5p, miR-187-5p, miR-16-5p, miR-92b-3p, miR-150-3p, miR-564, miR-125a-3p, miR-92b- 5p, miR-92a-3p, miR-663a, miR-4688, miR-4648, miR-6085, miR-6126, miR-6880-5p, miR-328-5p, miR-6768-5p, miR-3180, miR-6087, miR-1273g-3p, miR-1225-5p, miR-3196, miR-4695-5p, miR- 6732-5p, miR-638, miR-6813-5p, miR-665, miR-486-3p, miR-4466, miR-30c-1-3p, miR-3621, miR- 6743-5p, miR-4298, miR-4741, miR-3619-3p, miR-6824-5p, miR-5698, miR-371a-5p, miR-4488, miR-1233-5p, miR-4723-5p, miR-24-3p, miR-1238-5p, miR-4442, miR-3928-3p, miR-6716-5p, miR- 6089, miR-6124, miR-6778-5p, miR-557 and miR-6090. </pat:ClaimText> </pat:Claim> </pat:Claims>