MicroRNAs that regulate muscle cell proliferation and differentiation
View Patent ↗The presently disclosed subject matter provides methods and compositions for modulating gene expression in myocytes. Also provided are cells comprising the compositions of the presently disclosed subject matter.
1. A method for treating a muscle injury in a subject in need thereof comprising administering to the subject an isolated nucleic acid encoding miR-206, wherein the miR-206 comprises a nucleotide sequence at least 70% identical to SEQ ID NO: 3 and the sequence comprises a seed region of SEQ ID NO: 3.
2. The method of claim 1 , wherein the muscle injury results from a mechanical muscle trauma, a muscular degenerative disorder, or a combination thereof.
3. The method of claim 2 , wherein the muscular degenerative disorder is muscular dystrophy, motor neuron disease, inflammatory myopathy, neuromuscular junction disease, endocrine myopathy, or metabolic muscular disease.
4. The method of claim 3 , wherein the muscular dystrophy is Duchenne muscular dystrophy.
5. The method of claim 1 , wherein miR-206 comprises a nucleotide sequence of SEQ ID NO: 3.
6. The method of claim 1 , wherein the isolated nucleic acid is a miR-206 precursor molecule.
7. The method of claim 1 , wherein the nucleic acid is present in a vector.
8. The method of claim 7 , wherein the vector comprises:
(a) a promoter operatively linked to the nucleic acid encoding miR-206; and
(b) a transcription termination sequence.
9. The method of claim 8 , wherein the promoter is a tissue-specific promoter.
10. The method of claim 8 , wherein the tissue-specific promoter is a muscle creatine kinase promoter.
11. The method of claim 7 , wherein the vector is a viral vector.
12. The method of claim 11 , wherein the viral vector is a retrovirus vector.
13. The method of claim 11 , wherein the viral vector is an adenovirus vector.
14. The method of claim 1 , wherein the subject is a mammal.
15. A method for increasing myocyte differentiation or inhibiting myocyte proliferation comprising contacting a skeletal muscle progenitor cell in vitro with an isolated nucleic acid encoding miR-206 wherein the miR-206 comprises a nucleotide sequence at least 70% identical to SEQ ID NO: 3 and the sequence comprises a seed region of SEQ ID NO: 3.
16. The method of claim 15 , wherein miR-206 comprises a nucleotide sequence of SEQ ID NO: 3.
17. The method of claim 15 , wherein the isolated nucleic acid is a miR-206 precursor molecule.
18. The method of claim 15 , wherein the nucleic acid is present in a vector.
19. The method of claim 18 , wherein the vector comprises:
(a) a promoter operatively linked to the nucleic acid encoding miR-206; and
(b) a transcription termination sequence.
20. The method of claim 19 , wherein the promoter is a tissue-specific promoter.
21. The method of claim 19 , wherein the tissue-specific promoter is a muscle creatine kinase promoter.
22. The method of claim 18 , wherein the vector is a viral vector.
23. The method of claim 22 , wherein the viral vector is a retrovirus vector.
24. The method of claim 22 , wherein the viral vector is an adenovirus vector.
25. The method of claim 15 , wherein the skeletal muscle progenitor cell is a satellite cell.
26. The method of claim 15 , wherein Pax7 expression is reduced in the skeletal muscle progenitor cell following contact with the isolated nucleic acid encoding miR-206.
27. The method of claim 1 , wherein the miR-206 comprises a nucleotide sequence at least 80% identical to SEQ ID NO: 3.
28. The method of claim 1 , wherein the miR-206 comprises a nucleotide sequence at least 90% identical to SEQ ID NO: 3.