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c-Myc inhibits myoblast differentiation and promotes myoblast proliferation and muscle fibre hypertrophy by regulating the expression of its target genes, miRNAs and lincRNAs

文献类型： 外文期刊

作者： Luo, Wen 1 ; Chen, Jiahui 1 ; Li, Limin 1 ; Ren, Xueyi 1 ; Cheng, Tian 1 ; Lu, Shiyi 1 ; Lawal, Raman Akinyanju 4 ; Nie, 1 ;

作者机构： 1.South China Agr Univ, Dept Anim Genet Breeding & Reprod, Coll Anim Sci, Guangzhou 510642, Guangdong, Peoples R China

2.South China Agr Univ, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Minist Agr, Guangzhou 510642, Guangdong, Peoples R China

3.South China Agr Univ, Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou 510642, Guangdong, Peoples R China

4.Univ Nottingham, Cells Organisms & Mol Genet Div, Sch Life Sci, Nottingham NG7 2RD, England

期刊名称：CELL DEATH AND DIFFERENTIATION （ 影响因子：15.828； 五年影响因子：12.774 ）

ISSN： 1350-9047

年卷期： 2019 年 26 卷 3 期

页码：

收录情况： SCI

摘要： The transcription factor c-Myc is an important regulator of cellular proliferation, differentiation and embryogenesis. While c-Myc can inhibit myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that c-Myc does not only inhibits myoblast differentiation but also promotes myoblast proliferation and muscle fibre hypertrophy. By performing chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we identified the genome-wide binding profile of c-Myc in skeletal muscle cells. c-Myc achieves its regulatory effects on myoblast proliferation and differentiation by targeting the cell cycle pathway. Additionally, c-Myc can regulate cell cycle genes by controlling miRNA expression of which dozens of miRNAs can also be regulated directly by c-Myc. Among these c-Myc-associated miRNAs (CAMs), the roles played by c-Myc-induced miRNAs in skeletal muscle cells are similar to those played by c-Myc, whereas c-Myc-repressed miRNAs play roles that are opposite to those played by c-Myc. The cell cycle, ERK-MAPK and Akt-mediated pathways are potential target pathways of the CAMs during myoblast differentiation. Interestingly, we identified four CAMs that can directly bind to the c-Myc 3' UTR and inhibit c-Myc expression, suggesting that a negative feedback loop exists between c-Myc and its target miRNAs during myoblast differentiation. c-Myc also potentially regulates many long intergenic noncoding RNAs (lincRNAs). Linc-2949 and linc-1369 are directly regulated by c-Myc, and both lincRNAs are involved in the regulation of myoblast proliferation and differentiation by competing for the binding of muscle differentiation-related miRNAs. Our findings do not only provide a genome-wide overview of the role the c-Myc plays in skeletal muscle cells but also uncover the mechanism of how c-Myc and its target genes regulate myoblast proliferation and differentiation, and muscle fibre hypertrophy.

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