MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

Arch Physiol Biochem. 2022 Dec;128(6):1426-1433. doi: 10.1080/13813455.2020.1773862. Epub 2020 Jun 17.

Abstract

Several studies have suggested that fibroblast-like synoviocytes (FLSs) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the healthy synovial tissues and FLSs. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of cleaved-Caspase-3, -8 and -9. Furthermore, CCR4 was determined to target miR-6089 directly, and its expression was significantly increased in the synovial tissues of RA than in the healthy synovial tissues. The overexpression of CCR4 reversed the effect of miR-6089 on proliferation and apoptosis in RA-FLSs effectively. In conclusion, our study suggests that the miR-6089 may be a potential target for prevention and treatment of RA.

Keywords: CCR4; MiRNA-6089; fibroblast-like synoviocytes; rheumatoid arthritis.

MeSH terms

  • Apoptosis / genetics
  • Arthritis, Rheumatoid* / genetics
  • Arthritis, Rheumatoid* / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Receptors, CCR4 / metabolism
  • Synoviocytes* / metabolism
  • Synoviocytes* / pathology

Substances

  • MicroRNAs
  • Caspase 3
  • CCR4 protein, human
  • Receptors, CCR4