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

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 MST...

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Bibliographic Details
Published in:Acta biochimica et biophysica Sinica 2017-05, Vol.49 (5), p.392-399
Main Authors: Jia, Haixue, Zhao, Yixia, Li, Tingting, Zhang, Yong, Zhu, Dahai
Format: Article
Language:English
Subjects:
Aging - pathology
Aging - physiology
Animals
Cell Differentiation - physiology
Cell Line
Down-Regulation - physiology
Gene Expression Regulation, Developmental - physiology
Mice
Mice, Knockout
MicroRNAs - metabolism
Muscle Development - physiology
Muscle Fibers, Skeletal - classification
Muscle Fibers, Skeletal - cytology
Muscle Fibers, Skeletal - metabolism
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Myostatin - metabolism
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Summary: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 （Pgcla）, is a direct target of miR-30e. Overexpression of miR- 30e in C2C12 cells significantly decreased Pgcla and increased type II form of myosin heavy chain gene expression, suggesting that miR-30e functionally associates with glycolytic myofiber forma- tion. Thus, our data indicate that the altered fiber-type composition in MSTN-/- mice are attributable in part to deregulated expression of miR-30e.
ISSN:1672-9145
1745-7270
DOI:10.1093/abbs/gmx019