miR-30e is negatively regulated by myostatin in skeletal muscle and is functionally related to fiber-type composition

<span class="paragraphSection"><div class="boxTitle">Abstract</div>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 (<span style="font-style:italic;">Pgc1α</span>), is a direct target of miR-30e. Overexpression of miR-30e in C2C12 cells significantly decreased <span style="font-style:italic;">Pgc1α</span> 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.</span>

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