miR-410-3p regulates proliferation and apoptosis of fibroblast-like synoviocytes by targeting YY1 in rheumatoid arthritis

Biomed Pharmacother. 2019 Nov:119:109426. doi: 10.1016/j.biopha.2019.109426. Epub 2019 Sep 7.

Abstract

In our previous study, miR-410-3p had been confirmed to regulate inflammatory cytokine release in rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). However, other biological functions of miR-410-3p in RA FLSs still remain unexplored. In the present study, we focused on the effect of miR-410-3p on proliferation, apoptosis, and cell cycle of RA FLSs, and explored the potential underlying mechanism. miR-410-3p mRNA levels in the synovium and FLSs of patients with RA and of healthy controls were quantitated by RT-qPCR. The levels of miR-410-3p were reduced in both synovium and FLSs from patients with RA. Next, we focused on the roles of miR-410-3p in cell viability, apoptosis, and cell cycle, by transfecting miR-410-3p mimics and inhibitor into RA FLSs, and conducting CCK-8 assay, EdU staining and flow cytometry. Results showed that miR-410-3p up-regulation suppressed proliferation, promoted apoptosis and G1-S phase transition while miR-410-3p down-regulation had opposite effects. YY1 was verified as a direct target gene of miR-410-3p through the luciferase reporter system; YY1 up-regulation was able to rescue the effects of miR-410-3p in RA FLSs. Taken together, our current findings might provide a potential therapeutic target for RA.

Keywords: Apoptosis; Proliferation; Rheumatoid arthritis; microRNAs.

MeSH terms

  • Apoptosis / genetics*
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / pathology
  • Base Sequence
  • Cell Cycle / genetics
  • Cell Line
  • Cell Proliferation / genetics
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Synoviocytes / metabolism
  • Synoviocytes / pathology*
  • YY1 Transcription Factor / metabolism*

Substances

  • MIRN410 microRNA, human
  • MicroRNAs
  • YY1 Transcription Factor
  • YY1 protein, human