miR-9-5p 通过靶向 IGF2BP3 抑制 IGF2-PI3K/Akt 信号通路抑制骨骼肌卫星细胞增殖和分化。

miR-9-5p Inhibits Skeletal Muscle Satellite Cell Proliferation and Differentiation by Targeting IGF2BP3 through the IGF2-PI3K/Akt Signaling Pathway.

机构信息

Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Int J Mol Sci. 2020 Feb 28;21(5):1655. doi: 10.3390/ijms21051655.

Abstract

MicroRNAs are evolutionarily conserved, small non-coding RNAs that play critical post-transcriptional regulatory roles in skeletal muscle development. We previously found that miR-9-5p is abundantly expressed in chicken skeletal muscle. Here, we demonstrate a new role for miR-9-5p as a myogenic microRNA that regulates skeletal muscle development. The overexpression of miR-9-5p significantly inhibited the proliferation and differentiation of skeletal muscle satellite cells (SMSCs), whereas miR-9-5p inhibition had the opposite effect. We show that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is a target gene of miR-9-5p, using dual-luciferase assays, RT-qPCR, and Western Blotting, and that it promotes proliferation and differentiation of SMSCs. In addition, we found that IGF2BP3 regulates IGF-2 expression, using overexpression and knockdown studies. We show that Akt is activated by IGF2BP3 and is essential for IGF2BP3-induced cell development. Together, our results indicate that miR-9-5p could regulate the proliferation and differentiation of myoblasts by targeting IGF2BP3 through IGF-2 and that this activity results in the activation of the PI3K/Akt signaling pathway in skeletal muscle cells.

摘要

微小 RNA 是进化上保守的小非编码 RNA,在骨骼肌发育中发挥关键的转录后调控作用。我们之前发现 miR-9-5p 在鸡骨骼肌中大量表达。在这里,我们证明了 miR-9-5p 作为一种肌源性 microRNA 的新作用,它调节骨骼肌的发育。miR-9-5p 的过表达显著抑制骨骼肌卫星细胞(SMSCs)的增殖和分化,而 miR-9-5p 的抑制则产生相反的效果。我们通过双荧光素酶报告基因实验、RT-qPCR 和 Western Blotting 显示胰岛素样生长因子 2 mRNA 结合蛋白 3(IGF2BP3)是 miR-9-5p 的靶基因,并显示它促进 SMSCs 的增殖和分化。此外,我们发现 IGF2BP3 通过上调和下调研究调节 IGF-2 的表达。我们表明 Akt 被 IGF2BP3 激活,并且对于 IGF2BP3 诱导的细胞发育是必需的。总之,我们的结果表明,miR-9-5p 通过 IGF-2 靶向 IGF2BP3 来调节成肌细胞的增殖和分化,并且这种活性导致骨骼肌细胞中 PI3K/Akt 信号通路的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/375c/7084337/339e5bf11fe4/ijms-21-01655-g001.jpg

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