title: MicroRNA-139-5p regulates C2C12 cell myogenesis through blocking Wnt/β-catenin signaling pathway.
abstract: MicroRNAs (miRNAs) are novel and potent regulators in myogenesis. However, the molecular mechanisms that many miRNAs regulate myoblast proliferation and differentiation which are largely unknown. Here, we found that miR-139-5p increased during C2C12 myoblast proliferation, while presenting an inverse trend during C2C12 myoblast differentiation. Flow cytometry and EdU incorporation assay showed that miR-139-5p slowed down the growth of C2C12 cells. Additional study demonstrated that ectopic introduction of miR-139-5p into C2C12 cells blocked myoblast differentiation. Importantly, we demonstrated for the first time that Wnt1, which is associated with the Wnt/β-catenin signaling pathway, was a direct target of miR-139-5p. Moreover, we found that the expression level of Wnt1 was suppressed significantly (p < 0.01) by miR-139-5p, which triggered inhibition of Wnt/β-catenin signaling through upregulation of glycogen synthase kinase 3 beta (GSK-3β; p < 0.05) and downregulation of p-GSK-3β (p < 0.01), β-catenin (p < 0.05), and nuclear β-catenin (p < 0.01). Taken together, these results suggest that miR-139-5p is an important negative regulator in myogenesis through blocking the Wnt1-mediated Wnt/β-catenin signaling pathway.
authors.affiliation: a Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Mi
authors.forename: Youlei
authors.initials: Y
authors.lastname: Li
authors.forename: Qiangling
authors.initials: Q
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Gongshe
authors.initials: G
authors.lastname: Yang
authors.forename: Xueli
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3
keywords: C2C12; Wnt/β-catenin signaling pathway; différenciation des myoblastes; miR-139-5p; myoblast differentiation; myoblast proliferation; prolifération des myoblastes; voie de signalisation Wnt/caténine