Lnc-Malat1 通过海绵吸附 miR-129-5p 促进 C2C12 肌管向慢肌纤维型转化。
Lnc-Malat1 promotes slow myofiber-type transformation through sponging miR-129-5p in C2C12 myotubes.
机构信息
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Shaanxi, China.
Laboratory of Animal Fat Deposition & Muscle Development, College of Animal Science and Technology, Northwest A&F University, Shaanxi, China.
出版信息
Exp Cell Res. 2023 Oct 1;431(1):113761. doi: 10.1016/j.yexcr.2023.113761. Epub 2023 Aug 25.
Long non-coding metastasis-associated lung adenocarcinoma transcript (lnc-Malat1) emerges as a novel regulator in skeletal muscle development, while its function and the related mechanism is not fully revealed yet. In this study, knockdown of lnc-Malat1 by siRNA significantly inhibited the expression of myoblast marker genes (MyHC, MyoD, and MyoG) and slow muscle fiber marker genes (MyHC I), together with repressed expression of mitochondria-related genes COX5A, ACADM, CPTA1, FABP3, and NDUFA1. Overexpression of lnc-Malat1 exerted an opposite effect, promoting myoblast differentiation and slow muscle fiber formation. Dual luciferase reporter assay revealed a direct interaction between lnc-Malat1 and miR-129-5p, and overexpression of lnc-Malat1 significantly inhibited miR-129-5p expression, thereby elevating the expression of Mef2a, miR-129-5p target protein. In addition, enforced expression of lnc-Malat1 restored the inhibitory effect of miR-129-5p on myoblast differentiation and MyHC I expression. Taken together, our results suggest that lnc-Malat1 promotes myoblast differentiation, and maintains the slow muscle fiber phenotype via adsorbing miR-129-5p.
长链非编码转移相关肺腺癌转录物（lnc-Malat1）在骨骼肌发育中作为一种新的调节因子出现，但其功能及其相关机制尚未完全揭示。在这项研究中，通过 siRNA 敲低 lnc-Malat1 显著抑制成肌细胞标记基因（MyHC、MyoD 和 MyoG）和慢肌纤维标记基因（MyHC I）的表达，同时抑制与线粒体相关的基因 COX5A、ACADM、CPTA1、FABP3 和 NDUFA1 的表达。lnc-Malat1 的过表达则产生相反的效果，促进成肌细胞分化和慢肌纤维形成。双荧光素酶报告基因实验显示 lnc-Malat1 与 miR-129-5p 之间存在直接相互作用，lnc-Malat1 的过表达显著抑制 miR-129-5p 的表达，从而上调 Mef2a，即 miR-129-5p 的靶蛋白的表达。此外，lnc-Malat1 的强制表达恢复了 miR-129-5p 对成肌细胞分化和 MyHC I 表达的抑制作用。总之，我们的研究结果表明，lnc-Malat1 通过吸附 miR-129-5p 促进成肌细胞分化，并维持慢肌纤维表型。
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