title: Inhibition of miR-29 by TGF-beta-Smad3 signaling through dual mechanisms promotes transdifferentiation of mouse myoblasts into myofibroblasts.
abstract: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in regulating many biological processes, including myogenic differentiation and muscle development. miR-29 is a promoting factor during myogenesis but its full spectrum of impact on muscle cells has yet to be explored. Here we describe an analysis of miR-29 affected transcriptome in C2C12 muscle cells using a high throughput RNA-sequencing platform. The results reveal that miR-29 not only functions to promote myogenic differentiation but also suppresses the transdifferentiation of myoblasts into myofibroblasts. miR-29 inhibits the fibrogenic differentiation through down-regulating both extracellular matrix genes and cell adhesion genes. We further demonstrate that miR-29 is under negative regulation by TGF-beta (TGF-β)-Smad3 signaling via dual mechanisms of both inhibiting MyoD binding and enhancing Yin Yang 1 (YY1)-recruited Polycomb association. Together, these results identify miR-29 as a pleiotropic molecule in both myogenic and fibrogenic differentiation of muscle cells.
authors.affiliation: Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Lijun
authors.initials: L
authors.lastname: Wang
authors.forename: Leina
authors.initials: L
authors.lastname: Lu
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Huating
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D017570:MyoD Protein / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000378:metabolism*; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D063146:Polycomb-Group Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse