MiR-18 inhibitor promotes the differentiation of bovine skeletal muscle-derived satellite cells by increasing MEF2D expression

J Anim Sci. 2022 Nov 1;100(11):skac238. doi: 10.1093/jas/skac238.

Abstract

Skeletal muscle is composed of muscle fibers formed from myoblast differentiation. Recently, numerous researchers have demonstrated that microRNAs (miRNAs) play an essential role in modulating the proliferation and differentiation of myoblasts. Our previous study has shown that among the miR-17-92 cluster members, miR-17 and miR-20a together with miR-19b can efficiently promote the differentiation of murine C2C12 and bovine primary myoblasts. However, the role of miR-18 in this process remains elusive. In this study, we revealed that miR-18 inhibited the differentiation of bovine skeletal muscle-derived satellite cells (bMDSCs), whereas an miR-18 inhibitor significantly promoted cell differentiation (p < 0.001). Then, a target gene of miR-18 was found to be myocyte enhancer factor 2D (MEF2D), which is critical for myoblast differentiation. Furthermore, we found that the combination of the miR-18 inhibitor and miR-19 significantly improved the formation of bMDSCs-derived muscle fibers (p < 0.001). This study revealed the role of miR-18 in bovine skeletal muscle differentiation and contributed to the understanding of the regulatory mechanism of mammalian myogenic differentiation.

Plain language summary

Beef is a beneficial food source, and improving muscle yield and quality has become a hot topic in the beef industry. Therefore, our study aimed to explore effective methods to improve bovine muscle cell differentiation to increase beef production. The study revealed that microRNA-18 (miR-18) inhibitor could promote the differentiation of bovine skeletal muscle-derived satellite cells (bMDSCs) by increasing the expression of myocyte enhancer factor 2D (MEF2D), a critical gene for myoblast differentiation. Furthermore, we found that combined inhibitors of miR-18 and miR-19 could significantly improve bMDSCs differentiation. Our study demonstrated the role of a new regulatory factor that may enhance beef production level and contributed to elucidating the mechanism of muscle differentiation.

MeSH terms

  • Animals
  • Cattle
  • Cell Differentiation
  • Cell Proliferation / genetics
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / metabolism
  • Mammals / genetics
  • Mammals / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Muscle Development / genetics
  • Muscle, Skeletal / metabolism
  • Satellite Cells, Skeletal Muscle* / metabolism

Substances

  • MEF2 Transcription Factors
  • MicroRNAs