Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb
Cyclic stretch induced miR-146a upregulation delays C2C12 myogenic differentiation through inhibition of Numb
复制标题
循环拉伸诱导的 miR-146a 上调通过抑制 Numb 延迟 C2C12 肌原性分化
DOI：
10.1016/j.bbrc.2008.11.041
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发表时间：
2009-01-09
影响因子：
3.1
通讯作者：
Liu, Yanpu
中科院分区：
文献类型：
--
作者：
Kuang, Wei;Tan, Jiali;Liu, Yanpu
肌肉干细胞的增殖和分化必须受到内源性和外源性信号的密切调控，才能有效地再生和适应性反应。microRNA在转录后抑制水平上被认为是多种生物过程中的有效调节因子。在这项研究中，我们发现miR-146 a在5%延伸/10 cycles/min的48小时循环拉伸后显著上调。重要的是，miR-146被预测与Numb的3' UTR中的序列碱基配对，其通过抑制Notch信号传导促进卫星细胞向肌细胞分化。通过报告基因分析和外源表达实验，证实miR-146 a对Numb的表达有抑制作用。通过miR-146 a抑制miR-146 a挽救了Numb的表达，并以受损的增殖为代价促进了C2 C12的分化。因此，我们首次提出miR-146 a通过抑制Numb的表达来扭曲肌肉分化和增殖的平衡。(C)2008年爱思唯尔公司All rights reserved.
Proliferation and differentiation of muscle stem cells must be tightly regulated by intrinsic and extrinsic signals for effective regeneration and adaptive response. MicroRNAs have been implicated as potent regulators in diverse biological processes at the level of posttranscriptional repression. In this study, we found that miR-146a was significantly upregulated upon a 48-h cyclic stretch of 5% elongation/10cycles/min. Importantly, miR-146 was predicted to base-pair with sequences in the 3' UTR of Numb, which promotes satellite cell differentiation towards muscle cells by inhibiting Notch signaling. Through reporter assay and exogenous expression experiment, we confirmed Numb was inhibited by miR-146a. Inhibition of miR-146a by antago-miR-146a rescued the expression of Numb and facilitated the differentiation of C2C12 at a cost of compromised proliferation. Thus, for the first time, we propose a role of miR-146a in skewing the balance of muscle differentiation and proliferation through inhibiting the expression of Numb. (C) 2008 Elsevier Inc. All rights reserved.