| Background: During muscle postnatal muscle development and muscle regeneration after injury, activated muscle satellite cells initiate to proliferate, and then differentiate to form new muscle fibers. mi R-17-92 cluster is highly expressed at early stage of postnatal development and initial post-injury stage, while thereafter steadily reduced, suggesting mi R-17-92 may be involved in cell proliferation and differentiation. The mi R-17-92 cluster was initially identified as a human oncogene that promotes cell proliferation while its role involved in cell differentiation during skeletal muscle development and the mechanism of mi R-17-92 expression remain unclear.Objective: To test the hypothesis that mi R-17-92 participates to muscle development and explore the mechanism of mi R-17-92 transcriptional expression during myogenesis.Methods and Results: We measured mi R-17-92 cluster expression during three biological processes including porcine muscle development, mouse muscle regeneration and mouse myoblast myogenesis. The results showed that mi R-17-92 is down-regulated during muscle development and regeneration. Exogenous overexpression of mi R-17-92 promotes proliferation of mouse myoblasts while inhibits myotube formation. We further identified the actin-associated protein enigma homolog 1(ENH1) as the common target of mi R-17, mi R-20 a and mi R-92 a, which is required for the cytoplasmic sequestration of Id1 to promote myogenesis. Moreover, injection of Ad-mi R-20 a in tiabialia anterious(TA) muscle accelerates the myoblast proliferation but delays new muscle fibers formation. In addition, we provided evidence that the transcription factor E2F1 directly activate the promoter of mi R-17-92 in myoblast.Conclusions: Our studies identify mi R-17-92 as a critical regulator of muscle development, and these findings reveal a mechanism by which E2F1 modulated mi R-17-92 expression, and propose a model of mi R-17-92-ENH1-Id1 mediated myogenesis. |
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