miR-424(322)-5p targets Ezh1 to inhibit the proliferation and differentiation of myoblasts  

作　　者：Yongqi Yue Xinxin Feng Yige Jia Shujie Luo Menglei Jiang Jiandan Luo Yonglin Hua Jiyue Zhang Yaqiu Lin Jian Li Yan Xiong 

机构地区：[1]College of Animal&Veterinary Sciences,Southwest Minzu University,Chengdu 610041,China [2]Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization,Ministry of Education,Southwest Minzu University,Chengdu 610041,China [3]Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization,Sichuan Province,Southwest Minzu University,Chengdu 610041,China [4]Key Laboratory of Animal Science of the State Ethnic Affairs Commission,Southwest Minzu University,Chengdu 610041,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第3期472-483,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Natural Science Foundation of Sichuan Province(No.23NSFSC1804);the National Natural Sciences Foundation of China(No.31902154);the Fundamental Research Funds for the Central Universities,Southwest Minzu University(No.2021057).

摘　　要：The proliferation and differentiation of myoblasts are considered the key biological processes in muscle development and muscle-related diseases,in which the miRNAs involved remain incompletely understood.Previous research reported that miR-424(322)-5p is highly expressed in mouse skeletal muscle.Therefore,C2C12 cells are used as a model to clarify the effect of miR-424(322)-5p on the proliferation and differentiation of myoblasts.The data show that miR-424(322)-5p exhibits a decreasing trend upon myogenic differentiation.Overexpression of miR-424(322)-5p inhibits the proliferation of myoblasts,manifested by downregulation of proliferation marker genes(CCNB1,CCND2,and CDK4),decreased percentage of EdU^(+)cells,and reduced cell viability.In contrast,these phenotypes are promoted in myoblasts treated with an inhibitor of miR-424(322)-5p.Interestingly,its gain of function inhibits the expression of myogenic regulators,including MyoD,MyoG,MyHC,and Myf5.Additionally,immunofluorescence staining of MyHC and MyoD shows that overexpression of miR-424(322)-5p reduces the number of myotubes and decreases the myotube fusion index.Consistently,inhibition of its function mediated by an inhibitor promotes the expressions of myogenic markers and myotube fusion.Mechanistically,gene prediction and dual-luciferase reporter experiments confirm that enhancer of zeste homolog 1(Ezh1)is one of the targets of miR-424(322)-5p.Furthermore,knockdown of Ezh1 inhibits the proliferation and differentiation of myoblasts.Compared with NC and inhibitor treatment,inhibitor+si-EZH1 treatment rescues the phenotypes of proliferation and differentiation mediated by the miR-424(322)-5p inhibitor.Taken together,these data indicate that miR-424(322)-5p targets Ezh1 to negatively regulate the proliferation and differentiation of myoblasts.

关 键 词：DIFFERENTIATION Ezh1 miR-424(322)-5p MYOBLAST proliferation skeletal muscle 

分 类 号：R542.2[医药卫生—心血管疾病]