MicroRNA-214 Promotes Myogenic Differentiation by Facilitating Exit from Mitosis via Down-regulation of Proto-oncogene N-ras
MicroRNA-214 Promotes Myogenic Differentiation by Facilitating Exit from Mitosis via Down-regulation of Proto-oncogene N-ras
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MicroRNA-214 通过下调原癌基因 N-ras 促进有丝分裂退出，从而促进肌源分化
DOI：
10.1074/jbc.m110.115824
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发表时间：
2010-08-20
影响因子：
4.8
通讯作者：
Cheng, Steven Y.
中科院分区：
文献类型：
--
作者：
Liu, Jun;Luo, Xiao-ju;Cheng, Steven Y.
脊椎动物肌肉的分化是由一个复杂的转录因子网络协调的，需要增殖的肌原性前体不可逆地退出细胞周期。最近的研究表明，大量的microRNA在肌肉分化的许多方面发挥另一层控制作用。通过与3 '非翻译区中的短识别序列退火，microRNA通过翻译抑制或mRNA降解来减弱靶基因表达。在这里，我们表明，miR-214促进小鼠C2 C12成肌细胞的成肌分化在p21和myogenin诱导之前的一个步骤。用2 '-O-甲基化双链抑制剂阻断miR-214功能可使C2 C12细胞维持在活跃的细胞周期中，从而抑制肌源性分化。通过全局基因表达谱分析，我们将原癌基因N-ras确定为miR-214的靶点之一。此外，用小干扰RNA或腺病毒介导的强制表达操纵N-Ras水平分别增强或减弱miR-214的作用。因此，我们的数据揭示了一种新的microRNA介导的机制，控制生肌分化。
Vertebrate muscle differentiation is coordinated by an intricate network of transcription factors requiring proliferating myogenic precursors to withdraw irreversibly from the cell cycle. Recent studies have implicated a large number of microRNAs exerting another layer of control in many aspects of muscle differentiation. By annealing to short recognition sequences in the 3'-untranslated region, microRNAs attenuate target gene expression through translation repression or mRNA degradation. Here, we show that miR-214 promotes myogenic differentiation in mouse C2C12 myoblasts at a step preceding the induction of p21 and myogenin. Blocking miR-214 function with a 2'-O-methylated double-stranded inhibitor maintained C2C12 cells in the active cell cycle, thereby inhibiting the myogenic differentiation. By global gene expression profiling, we identified the proto-oncogene N-ras as one of miR-214 targets. Furthermore, manipulating the N-Ras level with small interfering RNA or adenovirus-mediated forced expression either augmented or attenuated the effect of miR-214, respectively. Thus, our data uncovered a novel microRNA-mediated mechanism that controls myogenic differentiation.