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核因子κB调节的微小RNA miR-195和miR-497通过靶向Igf1r、Insr和细胞周期蛋白基因抑制成肌细胞增殖。

The NF-κB-modulated microRNAs miR-195 and miR-497 inhibit myoblast proliferation by targeting Igf1r, Insr and cyclin genes.

作者信息

Wei Wei, Zhang Wei-Ya, Bai Jian-Bo, Zhang Hai-Xin, Zhao Yuan-Yuan, Li Xin-Yun, Zhao Shu-Hong

机构信息

Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.

出版信息

J Cell Sci. 2016 Jan 1;129(1):39-50. doi: 10.1242/jcs.174235. Epub 2015 Nov 13.

DOI:10.1242/jcs.174235
PMID:26567220
Abstract

MicroRNAs (miRNAs) play important roles in the development of skeletal muscle. In our previous study, expression of miR-195 and miR-497 were shown to be upregulated during muscle development in pigs. In this study, we investigated the roles of these two miRNAs in myogenesis and analyzed their transcriptional regulation. Our results showed that miR-195 and miR-497 were upregulated during muscle development and myoblast differentiation. Moreover, miR-195 and miR-497 inhibited proliferation but not differentiation in C2C12 cells. Further investigation revealed that Igf1r, Insr, Ccnd2 and Ccne1 were directly targeted by miR-195 and miR-497 in myoblasts. In addition, we confirmed that miR-195 and miR-497, which shared the similar expression profiling, were negatively regulated by nuclear factor κB (NF-κB) in both myoblasts and skeletal muscle tissue. Our data illustrate that the signaling pathway NF-κB-miR-195/497-Igf1r/Insr-Ccnd2/Ccne1 plays important roles in myogenesis. Our study provides novel evidence for the roles of miR-195 and miR-497 in muscle development.

摘要

微小RNA(miRNA)在骨骼肌发育中发挥着重要作用。在我们之前的研究中,miR-195和miR-497的表达在猪的肌肉发育过程中被证明是上调的。在本研究中,我们调查了这两种miRNA在肌生成中的作用,并分析了它们的转录调控。我们的结果表明,miR-195和miR-497在肌肉发育和成肌细胞分化过程中上调。此外,miR-195和miR-497抑制C2C12细胞的增殖,但不抑制其分化。进一步研究表明,Igf1r、Insr、Ccnd2和Ccne1在成肌细胞中是miR-195和miR-497的直接靶点。此外,我们证实,具有相似表达谱的miR-195和miR-497在成肌细胞和骨骼肌组织中均受到核因子κB(NF-κB)的负调控。我们的数据表明,NF-κB-miR-195/497-Igf1r/Insr-Ccnd2/Ccne1信号通路在肌生成中发挥重要作用。我们的研究为miR-195和miR-497在肌肉发育中的作用提供了新的证据。

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