NOVEL HUMAN MICRORNAS ASSOCIATED WITH CANCER
The invention provides new sequences for human microRNAs associated with cancer which may be used as molecular markers for cancer diagnostics or as therapeutic targets or agents.
1 . A compound which comprises a contiguous nucleobase sequence of between a total of 8 to 30 nucleobases, wherein the contiguous sequence is identical or complementary to a nucleotide sequence present in a nucleic acid sequence selected from the group consisting of SEQ ID NOS 538, 539, and 540.
2 . The compound according to claim 1 , wherein the contiguous nucleobase sequence is in the form of an oligonucleotide.
3 . The compound according to claim 1 , wherein the contiguous nucleotide sequence comprises at least one nucleotide analogue.
4 . The compound according to claim 2 , wherein the oligonucleotide comprises a total of less than 21 nucleobases.
5 . The compound according to claim 4 , wherein the oligonucleotide comprises a total of between 12 and 20 nucleobases.
6 . A conjugate comprising the compound according to claim 1 and at least one non-nucleobase moiety covalently attached thereto.
7 . A composition comprising a compound according to claim 1 or the conjugate according to claim 6 , and at least one pharmaceutically acceptable diluent, carrier, salt or adjuvant.
8 . The compound of claim 1 , wherein said compound is a detection probe.
9 . The compound of claim 8 , wherein the contiguous nucleobase sequence forms a recognition sequence which is able to specifically hybridize or is complementary to, a RNA selected from the group consisting of SEQ ID NOs: 538, 539, and 540.
10 . The compound of claim 8 , wherein the oligonucleotide comprises nucleoside analogues with regular spacing over part or the entire nucleobases sequence.
11 . The compound of claim 10 , wherein the regular spacing is a nucleotide analogue at every second, third or fourth nucleobase position, or combination thereof.
12 . A collection of detection probes which comprises at least one compound according to claim 8 , and at least one further detection probe.
13 . The collection of detection probes according to claim 12 , which comprises at least one detection probe pair, and optionally at least one further detection probe, wherein one first member of the detection probe pair specifically hybridizes to, or is complementary to, a mature miRNA selected from the odd numbered SEQ IDs No 1-407, or the SEQ IDs listed in the first column of table 3, and the second member of the detection probe pair hybridizes, or is complementary to, the corresponding pre-mature miRNA even numbered SEQ IDs NO 2-408, or the SEQ IDs listed in the second column of table 3, wherein either the first member of the detection probe pair is unable to specifically hybridize to, or is not complementary to, the pre-mature miRNA, and/or the second member of the detection probe pair is unable to specifically hybridze to, or is not complementary to, the mature miRNA.
14 . The collection of detection probes according to claim 13 , which comprises at least two of said nonidentical detection probe pairs.
15 . The collection of detection probes according to claim 12 , which comprises at least one further detection probe comprising a recognition sequence consisting of nucleobases, wherein the detection probe is able to specifically hybridze to at least one RNA selected from the group comprising: hsa mIR 21, hsa-Let 7i, hsa miR 101, hsa miR 145, hsa miR 9, hsa miR122a, hsa miR 128b, hsa miR 149, hsa miR 125a, hsa miR 143, hsa miR 136, and hsa-miR 205.
16 . The collection of detection probes according to claim 12 , which further comprises at least one detection probe comprising a recognition sequence consisting of nucleobases, wherein the detection probe is able to specifically hybridize to at least one mRNA or DNA sequence associated with cancer.
17 . The collection of detection probes according to claim 12 which comprises at least 5 detection probes.
18 . The collection of detection probes according to 17, which comprises at least 30 detection probes.
19 . A kit for the characterization of cancer, the kit comprising at least one compound according to claim 8 , or a collection of detection probes according to claim 12 .
20 . A kit according to claim 19 , wherein the kit is in the form of, or comprises, an oligonucleotide array.
21 . The compound according to claim 3 , wherein said nucleotide analogue is a LNA.
22 . The compound of claim 1 , wherein said compound has a total of 12 to 30 nucleobases.
23 . The compound of claim 1 , wherein said contiguous sequence is identical to a contiguous sequence present in a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 538, 539, and 540.
24 . The compound of claim 23 , wherein said compound comprises the sequence of SEQ ID NO: 538, 539, or 540.
25 . The compound of claim 23 , wherein said compound consists of the sequence of SEQ ID NO: 538, 539, or 540.
26 . The compound of claim 1 , wherein said contiguous sequence is complementary to a contiguous sequence present in a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 538, 539, and 540.
27 . The compound of claim 25 , wherein said compound comprises a sequence complementary to SEQ ID NO: 538, 539, or 540.
28 . The compound of claim 25 , wherein said compound consists of a sequence complementary to SEQ ID NO: 538, 539, or 540.