Oligomeric compounds and compositions for use in modulation of pri-miRNAs
Compounds, compositions and methods are provided for modulating the levels expression, processing and function of pri-miRNAs. In particular, methods and compounds are provided for the modulation of the levels, expression, processing or function of polycistronic pri-miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and pri-miRNAs. Further provided are methods for selectively modulating pri-miRNA levels in a cell. Also provided are methods for identifying oligomeric compounds that result in increase pri-miRNA levels when contacted with a cell.
1. A method of increasing the amount of pri-miR-21 in a cell comprising:
contacting the cell with an oligomeric compound comprising an oligonucleotide consisting of 15 to 30 linked nucleosides and having a nucleobase sequence selected from SEQ ID NOs: 57 to 60, 65 to 70, and 74, whereby the amount of pri-miR-21 in the cell is increased.
2. The method of claim 1 wherein the oligonucleotide consists of 17 to 25 linked nucleosides.
3. The method of claim 1 wherein the oligomeric compound consists of an oligonucleotide.
4. The method of claim 1 wherein at least one nucleoside of the oligonucleotide comprises a sugar modification.
5. The method of claim 4 wherein each nucleoside of the oligonucleotide comprises a sugar modification.
6. The method of claim 5 wherein the sugar modification is 2′-O-methoxyethyl.
7. The method of claim 1 wherein at least one internucleoside linkage is a modified internucleoside linkage.
8. The method of claim 1 wherein each internucleoside linkage is a modified internucleoside linkage.
9. The method of claim 8 wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
10. The method of claim 1 wherein the oligonucleotide comprises at least one cytosine, wherein the cytosine is a 5-methylcytosine.
11. The method of claim 10 wherein each cytosine is a 5-methylcytosine.