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 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.
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.
Haixue
H
Jia
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.
Yixia
Y
Zhao
Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
Tingting
T
Li
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.
Yong
Y
Zhang
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.
Dahai
D
Zhu
D000375:Aging / Q000473:pathology / Q000502:physiology; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism*; D055435:Myostatin / Q000378:metabolism*
D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse; C525912:Mstn protein, mouse; D055435:Myostatin
miR-30e; myofiber type; myogenesis; myostatin; transcriptional regulation