LncR-133a Suppresses Myoblast Differentiation by Sponging miR-133a-3p to Activate the FGFR1/ERK1/2 Signaling Pathway in Goats

Genes

Li Li¹  Yang Zhang¹  Cuiting Yang¹  Dandan Li¹  Tao Zhong²  Linjie Wang²  Hongping Zhang²  Siyuan Zhan² 

[1] Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China;Key Laboratory of Livestock and Poultry Multi-Omics, Ministry of Agriculture and Rural Affairs, College of Animal and Technology, Sichuan Agricultural University, Chengdu 611130, China;

关键词: lncR-133a;    muscle differentiation;    miR-133a-3p;    FGFR1;    goat;   

DOI  :  10.3390/genes13050818

来源: DOAJ

【 摘 要 】

Long noncoding RNAs (lncRNAs) are involved in a variety of biological processes and illnesses. While a considerable number of lncRNAs have been discovered in skeletal muscle to far, their role and underlying processes during myogenesis remain mostly unclear. In this study, we described a new functional lncRNA named lncR-133a. Gene overexpression and interference studies in goat skeletal muscle satellite cells (MuSCs) were used to establish its function. The molecular mechanism by which lncR-133a governs muscle differentiation was elucidated primarily using quantitative real-time PCR (qRT-PCR), Western blotting, dual-luciferase activity assays, RNA immunoprecipitation, biotin-labeled probe, and RNA fluorescence in situ hybridization analyses. LncR-133a was found to be substantially expressed in longissimus thoracis et lumborum muscle, and its expression levels changed during MuSC differentiation in goats. We validated that lncR-133a suppresses MuSC differentiation in vitro. Dual-luciferase reporter screening, Argonaute 2 (AGO2) RNA immunoprecipitation assays, biotin-labeled lncR-133a capture, and fluorescence in situ hybridization showed that lncR-133a interacted with miR-133a-3p. Additionally, miR-133a-3p facilitated MuSC differentiation, but lncR-133a reversed this effect. The luciferase reporter assay and functional analyses established that miR-133a-3p directly targets fibroblast growth factor receptor 1 (FGFR1). Moreover, lncR-133a directly reduced miR-133a-3p’s capacity to suppress FGFR1 expression, and positively regulated the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). In summary, our results suggested that lncR-133a suppresses goat muscle differentiation by targeting miR-133a-3p and activating FGFR1/ERK1/2 signaling pathway.

【 授权许可】

Unknown