Compositions and methods for modulating angiogenesis
The invention generally features compositions and methods that are useful for modulating angiogenesis.
1. A method of treating an apoptosis resistant neoplasm or chemo-resistant neoplasm in a subject, the method comprising:
(a) identifying a subject as having an apoptosis resistant neoplasm; and
(b) administering to the subject an effective amount of an inhibitory nucleic acid molecule complementary to at least a portion of a microRNA of the mir-17-92 cluster,
wherein the inhibitory antisense nucleic acid molecule comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
miR-17-5p: ACUACCUGCACuGUAAGCACUUUG;
(SEQ ID NO: 1)
mir-18a: UAUCUGCACUAGAUGCACCUUA;
(SEQ ID NO: 2)
mir-19a: UCAGUUUUGCAUAGAUUUGCACA;
(SEQ ID NO: 3)
mir-19b: UCAGUUUUGCAUGGAUUUGCACA;
(SEQ ID NO: 4)
mir-20a: CUACCUGCACUAUAAGCACUUUA;
(SEQ ID NO: 5)
and
mir-92-1: CAGGCCGGGACAAGUGCAAUA,
(SEQ ID NO: 6)
thereby treating the apoptosis resistant neoplasm or the chemo-resistant neoplasm.
2. A method of treating a neoplasm in a subject in need thereof, the method comprising:
(a) identifying a neoplasm having an increase in the expression of a thrombospondin type 1repeat (TSR) protein; and
(b) administering to the subject an effective amount of an inhibitory nucleic acid molecule complementary to at least a portion of a microRNA of the mir-17-92 cluster,
wherein the inhibitory antisense nucleic acid molecule comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
miR-17-5p: ACUACCUGCACuGUAAGCACUUUG;
(SEQ ID NO: 1)
mir-18a: UAUCUGCACUAGAUGCACCUUA;
(SEQ ID NO: 2)
mir-19a: UCAGUUUUGCAUAGAUUUGCACA;
(SEQ ID NO: 3)
mir-19b: UCAGUUUUGCAUGGAUUUGCACA;
(SEQ ID NO: 4)
mir-20a: CUACCUGCACUAUAAGCACUUUA;
(SEQ ID NO: 5)
and
mir-92-1: CAGGCCGGGACAAGUGCAAUA,
(SEQ ID NO: 6)
thereby treating the neoplasm.
3. A method of characterizing a neoplasia as amenable to treatment with the method of claim 2 , the method comprising assaying the expression of a microRNA encoded by the miR-17-92 cluster,
wherein the microRNA comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
miR-17-5p: ACUACCUGCACuGUAAGCACUUUG;
(SEQ ID NO: 1)
mir-18a: UAUCUGCACUAGAUGCACCUUA;
(SEQ ID NO: 2)
mir-19a: UCAGUUUUGCAUAGAUUUGCACA;
(SEQ ID NO: 3)
mir-19b: UCAGUUUUGCAUGGAUUUGCACA;
(SEQ ID NO: 4)
mir-20a: CUACCUGCACUAUAAGCACUUUA;
(SEQ ID NO: 5)
and
mir-92-1: CAGGCCGGGACAAGUGCAAUA.
(SEQ ID NO: 6)
4. The method of claim 1 , wherein the antisense nucleic acid molecule decreases the expression of the microRNA.
5. The method of claim 1 , wherein the microRNA is mir-19.
6. The method of claim 1 , wherein the microRNA is mir-18.
7. The method of claim 1 , wherein the antisense nucleic acid molecule is an siRNA.
8. The method of claim 2 , wherein the antisense nucleic acid molecule decreases the expression of the microRNA.
9. The method of claim 2 , wherein the microRNA is mir-19.
10. The method of claim 2 , wherein the microRNA is mir-18.
11. The method of claim 2 , wherein the antisense nucleic acid molecule is an siRNA.