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CDK9 Regulates Apoptosis of Myoblast Cells by Modulation of microRNA‐1 Expression

机译:CDK9通过调节MicroRNA-1表达来调节肌细胞细胞的凋亡

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ABSTRACT Cdk9 is the catalytic core of the positive transcription elongation factor b (P‐TEFb) and regulates transcriptional elongation factors by phosphorylation of RNA pol II. Apart from its role on myogenic gene expression, Cdk9 regulation of muscle‐specific microRNAs in the early stage of cardiomyogenesis is poorly understood. Here we demonstrate that Cdk9 not only regulates myogenic transcription factors, but also controls muscle‐specific microRNAs. During cardiac differentiation of mouse embryonic stem cells, high Cdk9 expression preceded up‐regulation of miR‐1. To investigate potential regulatory roles of Cdk9 on cardiac microRNAs and myogenesis genes, we overexpressed Cdk9 in myoblast C2C12 cells, which resulted in significant induction of miR‐1 and miR‐206, while miR‐133 was downregulated. Moreover, expression levels of MyoD and Srf , key regulators of myogenesis, also increased in cells with overexpression of Cdk9 . We further observed Cdk9 ‐mediated apoptosis in C2C12 cells corresponding to induction of miR‐1 expression levels. Thus, Cdk9 plays a complex role in myocyte progenitor differentiation and apoptosis by regulating myogenic protein and muscle‐specific microRNA expression. J. Cell. Biochem. 119: 547–554, 2018. ? 2017 Wiley Periodicals, Inc.
机译:摘要CDK9是阳性转录伸长因子B(P-TEFB)的催化核心,通过RNA POL II的磷酸化调节转录伸长因子。除了其对肌遗传基因表达的作用外,心肌发生早期肌肉特异性微小RORNA的CDK9调节很差。在这里,我们证明CDK9不仅调节肌原转录因子,而且还控制肌肉特异性的微大罗氏。在小鼠胚胎干细胞的心脏分化过程中,高CDK9表达前面的miR-1。为了探讨CDK9对心脏微小RORNAS和肌发育基因的潜在调节作用,我们过表达CDK9在肌细胞C2C12细胞中,导致MIR-1和MIR-206的显着诱导,而MIR-133被下调。此外,MyOD和SRF的表达水平,肌发育的关键调节剂,在具有过表达CDK9的细胞中也增加。我们进一步观察到CDK9介导的CO 2C12细胞凋亡,所述C2C12细胞对应于miR-1表达水平的诱导。因此,CDK9通过调节肌菌蛋白和肌肉特异性微瘤表达,在肌细胞祖细胞分化和细胞凋亡中起着复杂作用。 J.Cell。生物学习。 119:547-554,2018 2017年Wiley期刊,Inc。

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