miR-16 controls myoblast proliferation and apoptosis through directly suppressing Bcl2 and FOXO1 activities

文献类型： 外文期刊

第一作者： Nie, Qinghua

作者： Nie, Qinghua

作者机构：

关键词： miR-16;Myoblast proliferation;Apoptosis;FOXO1;Bcl2

期刊名称：BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS （ 影响因子：4.49； 五年影响因子：5.318 ）

ISSN：

年卷期：

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收录情况： SCI

摘要： Myogenesis mainly involves several steps including myoblast proliferation, differentiation, apoptosis and fusion. Except for muscle specific regulators, few miRNAs were proved to coordinate this complex process. Here, we reported that miR-16 inhibited myoblast proliferation and promoted myoblast apoptosis by directly targeting Bcl2 and FOXO1. The expression level of miR-16 was significantly decreased in the hypertrophic pectoral muscle compared to the normal pectoral muscle in chicken. In vitro, elevating miR-16 significantly inhibited myoblast proliferation and promoted myoblast apoptosis, resulting in about 11.2% cells arrested in G1 phase and 12.3% apoptotic cells in the early stage. Bioinformatic and biochemical analyses revealed Bcl2 and FOXO1 as direct targets of miR-16. Consist to the effect of miR-16 on myogenesis, specific inhibition of Bcl2 or FOXO1 significantly suppressed myoblast proliferation and induced myoblast apoptosis, indicating that both Bcl2 and FOXO1 contributed to miR-16 regulatory function in myogenesis. Interestingly, FOXO1, as the core target, mediated multiple growth-related pathways induced by miR-16 such as PI3K-AKT-MAPK and PI3K-AKT-mTOR. Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) revealed that 234 annotated genes bound by FOXO1 in the early-differentiated myoblasts, which were significantly enriched in myogenic proliferation, death and hypotrophy. Altogether, we proposed that miR-16 acted as a coordinated mediator to suppress myogenesis in avian through the control of myoblast proliferation and apoptosis. These findings have provided a novel mechanism whereby miR-16 represses Bcl2 and FOXO1 expression to maintain myoblast growth and skeletal muscle mass. (C) 2017 The Author(s). Published by Elsevier B.V.

分类号： Q7

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