MiR-222-3p Regulates the Proliferation and Differentiation of C2C12 Myoblasts by Targeting BTG2


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Abstract

MiR-222-3p has been implicated in tumor cell proliferation and has an important role in the differentiation and maturation of myogenic cells. However, its role in skeletal myoblast proliferation is still unclear. In this study, we found that miR-222-3p expression increases initially and then decreases during C2C12 myoblast proliferation. Using synthetic miRNA mimics and inhibitors in gain- or loss-of-function experiments, we showed that miR-222-3p overexpression in C2C12 cells promotes myoblast proliferation and represses myofiber formation, while miR-222-3p downregulation has the opposite effect. Using a prediction program, BTG2 was identified as a possible target gene of miR-222-3p. During myogenesis, miR-222-3p mimics repress BTG2 expression, while miR-222-3p inhibitors promote BTG2 expression. Using dual-luciferase reporter assay, we further demonstrated that miR-222-3p specifically targets BTG2. Additionally, we show that siRNA-mediated downregulation of BTG2 expression in C2C12 myoblasts promotes the proliferation and suppresses differentiation. In conclusion, we provide a novel insight into the mechanism by which miR-222-3p regulates the proliferation and differentiation of C2C12 myoblasts by targeting BTG2. This information contributes to our understanding of the role of miRNAs in skeletal muscle development.

About the authors

D. L. Yang

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

M. L. Gan

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

Y. Tan

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

G. H. Ge

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

Q. Li

Sichuan Province General Station of Animal Husbandry

Email: zhuli7508@163.com
China, Chengdu, 611130

Y. Z. Jiang

College of Life and Science, Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

G. Q. Tang

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

M. Z. Li

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

J. Y. Wang

Chongqing Academy of Animal Sciences

Email: zhuli7508@163.com
China, Chongqing, 402460

X. W. Li

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Email: zhuli7508@163.com
China, Chengdu, 611130

S. H. Zhang

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Author for correspondence.
Email: zhangsh1919@163.com
China, Chengdu, 611130

L. Zhu

Farm Animal Genetics Resources Exploration and Innovation Key Laboratory of Sichuan Province,
Sichuan Agricultural University

Author for correspondence.
Email: zhuli7508@163.com
China, Chengdu, 611130

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