Microrna compositions and methods

Abstract

Provided herein are compositions comprising oligomeric compounds. In certain embodiments, the oligomeric compounds are useful as miRNA mimics. The oligomeric compounds may mimic the activity of miR-34. Also provided herein are methods for the treatment of cancer.

1 . A method of treating cancer comprising administering to a subject having cancer a composition comprising an oligomeric compound comprising an oligonucleotide consisting of 7 to 30 linked nucleosides, wherein the nucleobase sequence of the oligonucleotide has at least 80% seed region identity with the nucleobase sequence of miR-34. 
     
     
         2 . The method of  claim 1  wherein the cancer is selected from liver cancer, breast cancer, lung cancer, colon cancer, ovarian cancer, cervical cancer, leukemia, lymphoma, brain cancer, esophageal cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, kidney cancer, melanoma, myeloma, oral cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, bladder cancer, thyroid cancer, and testicular cancer. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The method of  claim 1  wherein the subject is a human. 
     
     
         7 . The method of  claim 1  wherein the administering comprises intravenous administration, subcutaneous administration, intratumoral administration, or chemoembolization. 
     
     
         8 . The method of  claim 1  comprising administering at least one additional therapy. 
     
     
         9 . The method of  claim 8  wherein the at least one additional therapy comprises a chemotherapeutic agent and/or radiation therapy. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 9  wherein the chemotherapeutic agent is selected from 5-fluorouracil, gemcitabine, doxorubicine, mitomycin c, sorafenib, etoposide, carboplatin, epirubicin, irinotecan and oxaliplatin. 
     
     
         12 - 15 . (canceled) 
     
     
         16 . The method of  claim 1  wherein the administering results in reduction of tumor size, reduction of tumor number, prevention of an increase in tumor size, prevention of an increase in tumor number, prevention of metastasis, and/or reduction in the rate of metastasis. 
     
     
         17 - 21 . (canceled) 
     
     
         22 . The method of  claim 1  wherein the administering extends overall survival time of the subject and/or progression-free survival of the subject. 
     
     
         23 - 30 . (canceled) 
     
     
         31 . The method of  claim 1  wherein the cancer is a p53-expressing cancer. 
     
     
         32 . (canceled) 
     
     
         33 . A method of regulating seed-matched transcripts comprising contacting a cell with a composition comprising an oligomeric compound comprising an oligonucleotide consisting of 7 to 30 linked nucleosides, wherein the nucleobase sequence of the oligonucleotide has at least 80% seed region identity with the nucleobase sequence of miR-34. 
     
     
         34 . The method of any  claim 33 , wherein the miR-34 is miR-34a. 
     
     
         35 . The method of  claim 33  comprising down-regulating seed-matched transcripts. 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 33  comprising inducing apoptosis in the cell, inducing senescence in the cell, or inducing cell cycle arrest in the cell. 
     
     
         38 - 43 . (canceled) 
     
     
         44 . The method of  claim 1  wherein the cancer comprises cells which overexpress Myc and/or comprises cells which have a Myc mutation. 
     
     
         45 - 48 . (canceled) 
     
     
         49 . The method of  claim 1 , wherein the oligomeric compound comprises a complementary oligonucleotide hybridized to the oligonucleotide. 
     
     
         50 . The method of  claim 1 , wherein the oligonucleotide has the sequence of SEQ ID NO: 1. 
     
     
         51 . (canceled) 
     
     
         52 . The method of  claim 49 , wherein the complementary oligonucleotide comprises nucleobases 1 to 20 of SEQ ID NO: 7. 
     
     
         53 . The method of  claim 1 , wherein the composition comprises at least one lipid. 
     
     
         54 . The method of  claim 1 , wherein the composition comprises a cationic lipid, a neutral lipid, a sterol and a disaggregation lipid. 
     
     
         55 . (canceled) 
     
     
         56 . A composition comprising oligomeric compound comprising an oligonucleotide consisting of 7 to 30 linked nucleosides, wherein the nucleobase sequence of the oligonucleotide has at least 80% seed region identity with the nucleobase sequence of miR-34. 
     
     
         57 . The composition of  claim 56 , wherein the oligomeric compound comprises a complementary oligonucleotide hybridized to the oligonucleotide. 
     
     
         58 . The composition of  claim 56 , comprising at least one lipid. 
     
     
         59 - 61 . (canceled)