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miR-351-5p 通过直接靶向β-内酰胺酶调控 lnc-mg 来介导成肌分化

MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase-β and is regulated by lnc-mg.

机构信息

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.

College of Life and Science, Sichuan Agricultural University, Chengdu, China; and.

出版信息

FASEB J. 2019 Feb;33(2):1911-1926. doi: 10.1096/fj.201701394RRR. Epub 2018 Sep 14.

DOI:10.1096/fj.201701394RRR
PMID:30216112
Abstract

Skeletal muscle is an important and complex organ with a variety of functions in humans and animals. Skeletal myogenesis is a multistep and complex process, and increasing evidence suggests that microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) play critical roles in skeletal myogenesis. In this study the expression of miR-351-5p is dynamically regulated during skeletal myogenesis in vitro and in vivo. Cell-counting kit-8, qRT-PCR, and EdU immunofluorescence analysis showed that miR-351-5p overexpression promoted the proliferation and inhibited the differentiation of C2C12 myoblast, whereas inhibition of miR-351-5p had the opposite effect. In addition, miR-351-5p mediated the regulation of muscle fiber type transition in vivo. In vitro, loss of miR-351-5p in muscle tissues promoted muscle hypertrophy and increased slow-twitch fibers in the gastrocnemius muscles of mice. Luciferase reporter assay and functional analyses demonstrated that lactamase β ( LACTB) is a direct target of miR-351-5p involved in the regulation of skeletal myogenesis. Expression levels of a myogenesis-associated lncRNA ( lnc-mg) correlated negatively with miR-351-5p and positively with LACTB during C2C12 myoblast proliferation and differentiation. Further analyses showed that lnc-mg acted as a molecular sponge for miR-351-5p, demonstrating its involvement in the negative regulation of LACTB by miR-351-5p during skeletal myogenesis. These findings indicate that miRNA-351-5p functions in skeletal myogenesis by targeting LACTB and is regulated by lnc-mg, supporting the role of the competing endogenous RNA network in skeletal myogenesis.-Du, J., Zhang, P., Zhao, X., He, J., Xu, Y., Zou, Q., Luo, J., Shen, L., Gu, H., Tang, Q., Li, M., Jiang, Y., Tang, G., Bai, L., Li, X., Wang, J., Zhang, S., Zhu, L. MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase β and is regulated by lnc-mg.

摘要

骨骼肌是人体和动物中具有多种功能的重要而复杂的器官。骨骼肌发生是一个多步骤和复杂的过程,越来越多的证据表明 microRNAs (miRNAs) 和长链非编码 RNA (lncRNAs) 在骨骼肌发生中发挥关键作用。在这项研究中,miR-351-5p 的表达在体外和体内的骨骼肌发生过程中是动态调节的。细胞计数试剂盒-8、qRT-PCR 和 EdU 免疫荧光分析表明,miR-351-5p 的过表达促进了 C2C12 成肌细胞的增殖,抑制了分化,而抑制 miR-351-5p 则产生了相反的效果。此外,miR-351-5p 介导了体内肌纤维类型转换的调节。在体外,肌肉组织中 miR-351-5p 的缺失促进了肌肉肥大,并增加了小鼠腓肠肌中的慢收缩纤维。荧光素酶报告基因测定和功能分析表明,β-内酰胺酶 (LACTB) 是 miR-351-5p 调节骨骼肌发生的直接靶标。在 C2C12 成肌细胞增殖和分化过程中,与肌发生相关的 lncRNA (lnc-mg) 的表达水平与 miR-351-5p 呈负相关,与 LACTB 呈正相关。进一步的分析表明,lnc-mg 作为 miR-351-5p 的分子海绵发挥作用,表明其参与了 miR-351-5p 对骨骼肌发生过程中 LACTB 的负调控。这些发现表明,miRNA-351-5p 通过靶向 LACTB 来发挥作用,并受 lnc-mg 的调控,支持竞争内源性 RNA 网络在骨骼肌发生中的作用。

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