title: MicroRNA-761 regulates mitochondrial biogenesis in mouse skeletal muscle in response to exercise.
abstract: MicroRNAs (miRNAs) have been suggested to play critical roles in skeletal muscle in response to exercise. Previous study has shown that miR-761 was involved in a novel model regulating the mitochondrial network. However, its role in mitochondrial biogenesis remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-761 on mitochondrial biogenesis in skeletal muscle. Real-time quantitative PCR analysis demonstrated that aberrantly expressed miR-761 is involved in exercise activity and miR-761 is decreased by exercise training compared with the sedentary control mice. miR-761 suppresses mitochondrial biogenesis of C2C12 myocytes by targeting the 3'-UTR of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1α). Overexpression of miR-761 was capable of inhibiting the protein expression levels of PGC-1α. Moreover, miR-761 overexpression suppressed the p38 MAPK signaling pathway and down-regulated the expression of phosphorylated MAPK-activated protein kinase-2 (P-MK2), a downstream kinase of p38 MAPK. The phosphorylation of activating transcription factors 2 (ATF2) that plays a functional role in linking the activation of the p38 MAPK pathway to enhanced transcription of the PGC-1α was also inhibited by the overexpression of miR-761. These findings revealed a novel regulation mechanism for miR-761 in skeletal myocytes, and contributed to a better understanding of the modulation of skeletal muscle in response to exercise.
authors.affiliation: Affiliated Hospital of Hebei Engineering University, Handan, 056002, Hebei, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Medical College of Hebei Engineering University, Handan, 056002, Hebei, China.
authors.forename: Chaoxian
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Medical College of Hebei Engineering University, Handan, 056002, Hebei, China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Affiliated Hospital of Hebei Engineering University, Handan, 056002, Hebei, China. Electronic address: liuzhij1207@163.com.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Institute for Communicable Disease Control and Prevention (ICDC), Chinese Center for Disease Control and Prevention (China CDC), Beijing, 102206, China. Electronic address: zhangjianzhong@icdc.cn.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000235:genetics* / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D005082:Physical Exertion / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C000600165:MIRN761 microRNA, mouse; D035683:MicroRNAs; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors
keywords: MicroRNA-761; Mitochondrial biogenesis; PGC-1α; p38 MAPK