title: The NF-κB-modulated microRNAs miR-195 and miR-497 inhibit myoblast proliferation by targeting Igf1r, Insr and cyclin genes.
abstract: MicroRNAs (miRNAs) play important roles in the development of skeletal muscle. In our previous study, expression of miR-195 and miR-497 were shown to be upregulated during muscle development in pigs. In this study, we investigated the roles of these two miRNAs in myogenesis and analyzed their transcriptional regulation. Our results showed that miR-195 and miR-497 were upregulated during muscle development and myoblast differentiation. Moreover, miR-195 and miR-497 inhibited proliferation but not differentiation in C2C12 cells. Further investigation revealed that Igf1r, Insr, Ccnd2 and Ccne1 were directly targeted by miR-195 and miR-497 in myoblasts. In addition, we confirmed that miR-195 and miR-497, which shared the similar expression profiling, were negatively regulated by nuclear factor κB (NF-κB) in both myoblasts and skeletal muscle tissue. Our data illustrate that the signaling pathway NF-κB-miR-195/497-Igf1r/Insr-Ccnd2/Ccne1 plays important roles in myogenesis. Our study provides novel evidence for the roles of miR-195 and miR-497 in muscle development.
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Wei-Ya
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Bai
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Hai-Xin
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China xyli@mail.hzau.edu.cn.
authors.forename: Xin-Yun
authors.initials: XY
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000235:genetics* / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D024510:Muscle Development; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D056742:Cyclin D2; D019927:Cyclin E; C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D016328:NF-kappa B; C550139:mirn497 microRNA, mouse; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: Muscle; Myoblast; NF-κB; miR-195; miR-497