title: miR-378a-3p promotes differentiation and inhibits proliferation of myoblasts by targeting HDAC4 in skeletal muscle development.
abstract: Muscle development, or myogenesis, is a highly regulated, complex process. A subset of microRNAs (miRNAs) have been identified as critical regulators of myogenesis. Recently, miR-378a was found to be involved in myogenesis, but the mechanism of how miR-378a regulates the proliferation and differentiation of myoblasts has not been determined. We found that miR-378a-3p expression in muscle was significantly higher than in other tissues, suggesting an important effect on muscle development. Overexpression of miR-378a-3p increased the expression of MyoD and MHC in C2C12 myoblasts both at the level of mRNA and protein, confirming that miR-378a-3p promoted muscle cell differentiation. The forced expression of miR-378a-3p promoted apoptosis of C2C12 cells as evidenced by CCK-8 assay and Annexin V-FITC/PI staining results. Through TargetScan, histone acetylation enzyme 4 (HDAC4) was identified as a potential target of miR-378a-3p. We confirmed targeting of HDAC4 by miR-378a-3p using a dual luciferase assay and western blotting. Our RNAi analysis results also showed that HDAC4 significantly promoted differentiation of C2C12 cells and inhibited cell survival through Bcl-2. Therefore, we conclude that miR-378a-3p regulates skeletal muscle growth and promotes the differentiation of myoblasts through the post-transcriptional down-regulation of HDAC4.
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wei
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Dong
authors.initials: D
authors.lastname: Dong
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Lan
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Huang
authors.affiliation: b Animal Health Supervision in Henan Province , Zhengzhou , Henan , China.
authors.forename: Yueyu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: c Bureau of Animal Husbandry of Biyang County , Biyang , Henan , China.
authors.forename: Fengpeng
authors.initials: F
authors.lastname: Lin
authors.affiliation: d Bureau of Animal Husbandry of Suibin County , Suibin , Heilongjiang , China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a Shaanxi Key Laboratory of Agricultural Molecular Biology, College of Animal Science and Technology, Northwest A&F University , Yangling , Shaanxi , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D011401:Promoter Regions, Genetic
chemical_list: D020413:3' Untranslated Regions; C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases
keywords: Cell apoptosis; HDAC4; cell proliferation; miR-378a-3p; muscle differentiation