MiR-208b regulates cell cycle and promotes skeletal muscle cell proliferation by targeting CDKN1A

J Cell Physiol. 2019 Apr;234(4):3720-3729. doi: 10.1002/jcp.27146. Epub 2018 Oct 14.

Abstract

Skeletal muscle is the most abundant tissue in the body. The development of skeletal muscle cell is complex and affected by many factors. A sea of microRNAs (miRNAs) have been identified as critical regulators of myogenesis. MiR-208b, a muscle-specific miRNA, was reported to have a connection with fiber type determination. However, whether miR-208b has effect on proliferation of muscle cell was under ascertained. In our study, cyclin-dependent kinase inhibitor 1A (CDKN1A), which participates in cell cycle regulation, was predicted and then validated as one target gene of miR-208b. We found that overexpression of miR-208b increased the expression of cyclin D1, cyclin E1, and cyclin-dependent kinase 2 at the levels of messenger RNA and protein in cattle primary myoblasts in vivo and in vitro. Flow cytometry showed that forced expression of miR-208b increased the percentage of cells at the S phase and decreased the percentage of cells at the G0/G1 phase. These results indicated that miR-208b participates in the cell cycle regulation of cattle primary myoblast cells. 5-Ethynyl-20-deoxyuridine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that overexpression of miR-208b promoted the proliferation of cattle primary myoblasts. Therefore, we conclude that miR-208b participates in the cell cycle and proliferation regulation of cattle primary skeletal muscle cell through the posttranscriptional downregulation of CDKN1A.

Keywords: CDKN1A; cell cycle; cell proliferation; miR-208b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Binding Sites
  • Cats
  • Cell Cycle*
  • Cell Differentiation
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Disease Models, Animal
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscular Diseases / genetics
  • Muscular Diseases / metabolism*
  • Muscular Diseases / pathology
  • Myoblasts, Skeletal / metabolism*
  • Myoblasts, Skeletal / pathology
  • RNA Processing, Post-Transcriptional
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • MicroRNAs
  • Mirn208 microRNA, mouse