MicroRNA-17-92 regulates myoblast proliferation and differentiation by targeting the ENH1/Id1 signaling axis.
MicroRNA-17-92 regulates myoblast proliferation and differentiation by targeting the ENH1/Id1 signaling axis.
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MicroRNA-17-92 通过靶向 ENH1/Id1 信号轴调节成肌细胞增殖和分化
DOI：
10.1038/cdd.2016.56
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发表时间：
2016-10
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
肌肉发生是骨骼肌再生和出生后生长过程中的重要生物学过程。越来越多的证据表明microRNAs(MiRNAs)在肌肉发生中的关键作用。我们对miRNA表达模式的分析表明，miR-17-92簇的miRNAs在肌肉发生刺激后在C2C12细胞中显著下调，在小鼠骨骼肌损伤后强烈诱导，此后稳步下降，并在小鼠和猪出生后的生长过程中随着年龄的增长而下调。然而，它们在肌肉发育过程中的作用仍然难以捉摸。我们发现miR-17-92簇促进了小鼠成肌细胞的增殖，但抑制了肌管的形成。MIR-17、-20a和-92a针对肌动蛋白相关蛋白同源1(ENH1)。ENH1的沉默增加了分化抑制因子1(Id1)的核积聚，抑制了肌源性分化。此外，将表达miR-20a的腺病毒注射到胫骨前肌可下调ENH1并延迟再生。此外，在肌肉发生过程中miR-17-92的下调是由E2F1转录调节的。总体而言，我们的结果揭示了E2F1/miR-17-92/ENH1/Id1在肌肉发生过程中的调节轴。
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.
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