MicroRNA-17-92 regulates myoblast proliferation and differentiation by targeting the ENH1/Id1 signaling axis.
Myogenesis is an important biological process that occurs during both skeletal muscle regeneration and postnatal growth. Growing evidence points to the critical role of microRNAs (miRNAs) in myogenesis. Our analysis of miRNA expression patterns reveal that miRNAs of miR-17-92 cluster are dramatically downregulated in C2C12 cells after myogenesis stimulation, are strongly induced in mouse skeletal muscle after injury and decrease steadily thereafter and are downregulated with age in skeletal muscle during mouse and porcine postnatal growth. However, their roles in muscle developmental processes remain elusive. We show that the miR-17-92 cluster promotes mouse myoblast proliferation but inhibits myotube formation. miR-17, -20a and -92a target the actin-associated protein enigma homolog 1 (ENH1). The silencing of ENH1 increased the nuclear accumulation of the inhibitor of differentiation 1 (Id1) and represses myogenic differentiation. Furthermore, the injection of adenovirus expressing miR-20a into the tibialia anterior muscle downregulates ENH1 and delays regeneration. In addition, the downregulation of miR-17-92 during myogenesis is transcriptionally regulated by E2F1. Overall, our results reveal a E2F1/miR-17-92/ENH1/Id1 regulatory axis during myogenesis.
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.|Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
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H
Qiu
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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0000-0002-4811-4897
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Liu
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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Luo
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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J
Zhong
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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Z
Tang
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, Guangdong 518000, China.
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Kang
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
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Qu
Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, Guangdong 518060, China.
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W
Peng
Department of Physiological Sciences, Oklahoma State University, Stillwater, OK 74078, USA.
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Liu
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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Li
Shenzhen Key Laboratory of Microbial Genetic Engineering, College of Life Sciences, Shenzhen University, Shenzhen, Guangdong 518060, China.
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Gou
D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000378:metabolism; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D012038:Regeneration; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism
D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D050687:E2F1 Transcription Factor; C510085:ENH protein, mouse; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; C575895:MIRN17-92 microRNA, mouse; D035683:MicroRNAs; D008840:Microfilament Proteins