Myostatin (MSTN) negatively regulates skeletal myogenesis in which microRNAs (miRNAs) also play critical roles.Using miRNA microarrays of skeletal muscle from MSTN-knockout (MSTN-/-)mice,we recently showed that miR-431 is regulated by MSTN signaling.To identify additional miRNAs regulated by MSTN,we re-analyzed these miRNA arrays and validated their expression by quantitative RT-PCR.Herein,we demonstrated that miR-30e was significantly upregulated in skeletal muscle of MSTN-/-mice compared with that of the wild-type littermates.Importantly,the predicted targets of miR-30e are functionally involved in myocyte differentiation and fiber-type formation.Using luciferase reporter gene assays,we further showed that peroxisome proliferator-activated receptor gamma,coactivator 1 alpha (Pgc1α),is a direct target of miR-30e.Overexpression of miR30e in C2C12 cells significantly decreased Pgc1α and increased.type Ⅱ form of myosin heavy chain gene expression,suggesting that miR-30e functionally associates with glycolytic myofiber formation.Thus,our data indicate that the altered fiber-type composition in MSTN-/-mice are attributable in part to deregulated expression of miR-30e.
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