IGF-II is regulated by microRNA-125b in skeletal myogenesis.

IGF-II is regulated by microRNA-125b in skeletal myogenesis.
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DOI:
10.1083/jcb.201007165
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发表时间:
2011-01-10
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Chen J
Chen J
中科院分区:
其他
文献类型:
--
作者:
Ge Y;Sun Y;Chen J

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miR - 125b被鉴定为一种生肌性微小RNA(miRNA),它在哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的调控下,通过靶向胰岛素样生长因子 - II(IGF - II)来调节骨骼肌分化。 微小RNA(miRNAs)已成为骨骼肌生成的关键调节因子,但我们对生肌性miRNAs及其靶标的了解仍然有限。在这项研究中,我们报道了一种新型生肌性miRNA——miR - 125b的鉴定和特性。我们发现miR - 125b的水平在肌生成过程中下降,并且miR - 125b在体外培养的成肌细胞分化以及小鼠肌肉再生过程中起负向调节作用。我们的研究结果确定了IGF - II(胰岛素样生长因子2)——骨骼肌生成的关键调节因子,是miR - 125b在肌细胞和再生肌肉中的直接且主要的靶标,首次揭示了一种调控IGF - II表达的miRNA机制。此外,我们提供的证据表明,在体外和体内,miR - 125b的生物发生都受到不依赖激酶的哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的负向调控,这是mTOR调节IGF - II产生的双重机制的一部分,而IGF - II是控制骨骼肌生成起始的主要开关。
miR-125b is identified as a myogenic miRNA that regulates skeletal muscle differentiation by targeting IGF-II under the control of mTOR signaling. MicroRNAs (miRNAs) have emerged as key regulators of skeletal myogenesis, but our knowledge of the identity of the myogenic miRNAs and their targets remains limited. In this study, we report the identification and characterization of a novel myogenic miRNA, miR-125b. We find that the levels of miR-125b decline during myogenesis and that miR-125b negatively modulates myoblast differentiation in culture and muscle regeneration in mice. Our results identify IGF-II (insulin-like growth factor 2), a critical regulator of skeletal myogenesis, as a direct and major target of miR-125b in both myocytes and regenerating muscles, revealing for the first time an miRNA mechanism controlling IGF-II expression. In addition, we provide evidence suggesting that miR-125b biogenesis is negatively controlled by kinase-independent mammalian target of rapamycin (mTOR) signaling both in vitro and in vivo as a part of a dual mechanism by which mTOR regulates the production of IGF-II, a master switch governing the initiation of skeletal myogenesis.
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