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

Haixue Jia, Yixia Zhao, Tingting Li, Yong Zhang, and Dahai Zhu

The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, China

Acta Biochim Biophys Sin 2017, 49: 392–399; doi: 10.1093/abbs/gmx019

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 miR-30e 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.

miR-30e is upregulated in skeletal muscle of MSTN−/− mice

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