CircCSDE1 Regulates Proliferation and Differentiation of C2C12 Myoblasts by Sponging miR-21-3p

Int J Mol Sci. 2022 Oct 10;23(19):12038. doi: 10.3390/ijms231912038.

Abstract

The growth and development of skeletal muscle is regulated by many factors, and recent studies have shown that circular RNAs (circRNAs) can participate in this process. The model of porcine skeletal muscle injury was constructed to search for circRNAs that can regulate the growth and development of skeletal muscle in pigs. Using whole-transcriptome sequencing and bioinformatics analysis, a novel circRNA (circCSDE1) was screened out, which is highly expressed in skeletal muscle. Functional studies in C2C12 cells demonstrated that circCSDE1 could promote proliferation and inhibit myoblast differentiation, while opposing changes were observed by circCSDE1 knockdown. A dual-luciferase reporter assay revealed that circCSDE1 directly targeted miR-21-3p to regulate the expression of the downstream target gene (Cyclin-dependent kinase 16, CDK16). Moreover, miR-21-3p could inhibit proliferation and promote myoblast differentiation in C2C12 cells, opposite with the effects of circCSDE1. Additionally, the rescue experiments offered further evidence that circCSDE1 and its target, miR-21-3p, work together to regulate myoblast proliferation and differentiation. This study provides a theoretical basis for further understanding the regulatory mechanisms of circRNAs.

Keywords: C2C12; circCSDE1; differentiation; pig; proliferation; skeletal muscle injury.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinases / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle Development / genetics
  • Myoblasts / metabolism
  • RNA, Circular* / genetics
  • Swine

Substances

  • MicroRNAs
  • RNA, Circular
  • Cyclin-Dependent Kinases

Grants and funding

This work was supported by the National Natural Science Foundation of China (31872336; 32272846); Special Funds for Scholars Support Program of Shanxi Province (2016; 2017); Earmarked fund for Modern Agro-industry Technology Research System; Key Research and Development Project of Shanxi Province; Basic Research Project of Shanxi Province (201901D211376); Shanxi Agricultural University Science and Technology Innovation Fund under Grant (2018YJ35), and Shanxi Province Outstanding Doctor Award Fund (SXYBKY2018012).