title: Myostatin regulates miR-431 expression via the Ras-Mek-Erk signaling pathway.
abstract: MicroRNAs (miRNAs) play critical regulatory roles in controlling myogenic development both in vitro and in vivo; however, the molecular mechanisms underlying transcriptional regulation of miRNA genes in skeletal muscle cells are largely unknown. Here, using a microarray hybridization approach, we identified myostatin-regulated miRNA genes in skeletal muscle tissues by systematically searching miRNAs that are differentially expressed between wild-type and myostatin-null mice during development. We found that 116 miRNA genes were differentially expressed in muscles between these mice across different developmental stages. We further characterized myostatin-regulated miR-431 was upregulated in skeletal muscle tissues of myostatin-null mice. In functional studies, we found that overexpression of miR-431 in C2C12 myoblast cells attenuated myostatin-induced suppression of myogenic differentiation. Mechanistic studies further demonstrated that myostatin acted through the Ras-Mek-Erk signaling pathway to transcriptionally regulate miR-431 expression C2C12 cells. Our findings provide new insight into the mechanisms underlying transcriptional regulation of miRNA genes by myostatin during skeletal muscle development.
authors: 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, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors: Rimao
authors: R
authors: Wu
authors: 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, 5 Dong Dan San Tiao, Beijing 100005, PR China.
authors: Hu
authors: H
authors: Li
authors: Department of Biomedical Informatics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, PR China.
authors: Tingting
authors: T
authors: Li
authors: 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, 5 Dong Dan San Tiao, Beijing 100005, PR China. Electronic address: dr_zhangyong@126.com.
authors: Yong
authors: Y
authors: Zhang
authors: 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, 5 Dong Dan San Tiao, Beijing 100005, PR China. Electronic address: dhzhu@pumc.edu.cn.
authors: Dahai
authors: D
authors: Zhu
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018631:ras Proteins / Q000378:metabolism
chemical_list: C000599703:MIRN431 microRNA, mouse; D035683:MicroRNAs; D055435:Myostatin; D018631:ras Proteins
keywords: Myogenic differentiaion; Myostatin; Ras/Mek/Erk pathway; Transcriptional regulation; miR-431