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LncIRS1 controls muscle atrophy via sponging miR-15 family to activate IGF1-PI3K/AKT pathway

文献类型： 外文期刊

作者： Li, Zhenhui 1 ; Cai, Bolin 1 ; Abdalla, Bahareldin Ali 1 ; Zhu, Xuenong 1 ; Zheng, Ming 1 ; Han, Peigong 1 ; Nie, Qing 1 ;

作者机构： 1.South China Agr Univ, Dept Anim Genet Breeding & Reprod, Coll Anim Sci, Guangzhou 510642, Guangdong, Peoples R China

2.Minist Agr, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Guangzhou, Guangdong, Peoples R China

3.Minist Agr, Key Lab Chicken Genet Breeding & Reprod, Guangzhou, Guangdong, Peoples R China

4.Nanchang Normal Univ, Inst Biotechnol, Nanchang 330032, Jiangxi, Peoples R China

关键词： Atrophy; ceRNA; IRS1; Myogenesis; lncRNA-miRNA-gene network

期刊名称：JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE （ 影响因子：12.91； 五年影响因子：12.911 ）

ISSN： 2190-5991

年卷期： 2019 年 10 卷 2 期

页码：

收录情况： SCI

摘要： Background Recent studies indicate important roles for long noncoding RNAs (lncRNAs) in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of lncRNAs in skeletal muscle atrophy is still unclear. Our study aimed to identify the function of lncRNAs that control skeletal muscle myogenesis and atrophy. Methods RNA sequencing was performed to identify the skeletal muscle transcriptome (lncRNA and messenger RNA) between hypertrophic broilers and leaner broilers. To study the 'sponge' function of lncRNA, we constructed a lncRNA-microRNA (miRNA)-gene interaction network by integrated our previous submitted skeletal muscle miRNA sequencing data. The primary myoblast cells and animal model were used to assess the biological function of the lncIRS1 in vitro or in vivo. Results We constructed a myogenesis-associated lncRNA-miRNA-gene network and identified a novel ceRNA lncRNA named lncIRS1 that is specifically enriched in skeletal muscle. LncIRS1 could regulate myoblast proliferation and differentiation in vitro, and muscle mass and mean muscle fibre in vivo. LncIRS1 increases gradually during myogenic differentiation. Mechanistically, lncIRS1 acts as a ceRNA for miR-15a, miR-15b-5p, and miR-15c-5p to regulate IRS1 expression, which is the downstream of the IGF1 receptor. Overexpression of lncIRS1 not only increased the protein abundance of IRS1 but also promoted phosphorylation level of AKT (p-AKT) a central component of insulin-like growth factor-1 pathway. Furthermore, lncIRS1 regulates the expression of atrophy-related genes and can rescue muscle atrophy. Conclusions The newly identified lncIRS1 acts as a sponge for miR-15 family to regulate IRS1 expression, resulting in promoting skeletal muscle myogenesis and controlling atrophy.

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