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环状 RNA ACTA1 通过 MAP3K11/MAP2K7/JNK 通路作为 miR-199a-5p 和 miR-433 的海绵调节牛肌细胞发育。

Circular RNA ACTA1 Acts as a Sponge for miR-199a-5p and miR-433 to Regulate Bovine Myoblast Development through the MAP3K11/MAP2K7/JNK Pathway.

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, Yangling, Xianyang, Shaanxi 712100, China.

College of Grassland Agriculture, Northwest A&F University, Yangling, Xianyang, Shaanxi 712100, China.

出版信息

J Agric Food Chem. 2022 Mar 16;70(10):3357-3373. doi: 10.1021/acs.jafc.1c07762. Epub 2022 Mar 2.

Abstract

Circular RNAs (circRNAs) are a special class of noncoding RNA molecules that regulate many different biological processes. Myogenesis, a complex process, is primarily regulated by myogenic regulatory factors (MRFs) and various noncoding RNAs. However, the functions and regulatory mechanisms of circRNAs in myoblast development are unclear. In this study, we analyzed circRNA sequencing data of bovine myocyte tissues and identified circACTA1. Functional assays showed that circACTA1 could inhibit bovine myocyte proliferation and promote cell apoptosis and cytodifferentiation. In addition, circACTA1 could promote muscle repair in vivo. Mechanistically, luciferase assay and RNA immunoprecipitation were used to examine the interaction between circACTA1, miR-199a-5p, miR-433, and the target genes MAP3K11 and MAPK8. Meanwhile, we found that miR-199a-5p and miR-433 could suppress the expression of MAP3K11 and MAPK8, respectively. However, circACTA1 could mitigate this effect and activate the JNK signaling pathway. In conclusion, our results suggest that circACTA1 regulates the multiplication, apoptosis, and cytodifferentiation of bovine myocytes by competitively combining with miR-199a-5p and miR-433 to activate the mitogen-activated protein kinase kinase kinase 11 (MAP3K11)/mitogen-activated protein kinase kinase 7 (MAP2K7)/JNK signaling pathway.

摘要

环状 RNA(circRNAs)是一类特殊的非编码 RNA 分子,调节许多不同的生物过程。肌发生是一个复杂的过程,主要受肌生成调节因子(MRFs)和各种非编码 RNA 调节。然而,circRNAs 在成肌细胞发育中的功能和调控机制尚不清楚。在这项研究中,我们分析了牛肌细胞组织的 circRNA 测序数据,鉴定出 circACTA1。功能测定表明,circACTA1 可以抑制牛肌细胞增殖,促进细胞凋亡和细胞分化。此外,circACTA1 可以促进体内肌肉修复。机制上,通过荧光素酶测定和 RNA 免疫沉淀实验,检测了 circACTA1、miR-199a-5p、miR-433 与靶基因 MAP3K11 和 MAPK8 之间的相互作用。同时,我们发现 miR-199a-5p 和 miR-433 可以分别抑制 MAP3K11 和 MAPK8 的表达。然而,circACTA1 可以减轻这种作用,并激活 JNK 信号通路。总之,我们的研究结果表明,circACTA1 通过与 miR-199a-5p 和 miR-433 竞争结合,激活丝裂原活化蛋白激酶激酶激酶 11(MAP3K11)/丝裂原活化蛋白激酶激酶 7(MAP2K7)/JNK 信号通路,调节牛肌细胞的增殖、凋亡和细胞分化。

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