miR-212-3p reduced proliferation, and promoted apoptosis of fibroblast-like synoviocytes via down-regulating SOX5 in rheumatoid arthritis

Eur Rev Med Pharmacol Sci. 2018 Jan;22(2):461-471. doi: 10.26355/eurrev_201801_14196.

Abstract

Objective: Several microRNAs have been reported to contribute the progression of rheumatoid arthritis (RA) due to the ectopic expression of miRNAs in fibroblast-like synoviocytes (FLS). However, the function of miR-212-3p in RA still has not been mentioned before.

Patients and methods: We obtained serum, synovial tissues, and FLS samples from RA patients and normal donors. Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to analysis the expression level of miR-212-3p. By using miR-212-3p mimics and inhibitors, we detected the effects of miR-212-3p on cell proliferation, cell cycle, and apoptosis in RA-FLS. Dual-luciferase and Western-blot were employed to verify the target of miR-212-3p. In addition, we over-expressed the SOX5 in miR-212-3p mimics treatment FLS to emphasize our results.

Results: The level of miR-212-3p in serum, synovial tissues, and FLS from RA patients was lower than these in relative normal group. Up-regulation of miR-212-3p inhibited cell proliferation, promoted cell apoptosis; however, knockdown of miR-212-3p promoted cell growth but reduced cell apoptotic rate. Furthermore, we found SOX5 as a direct target of miR-212-3p in RA-FLS and up-regulation of SOX5 reversed the effects of miR-212-3p over-expression.

Conclusions: miR-212-3p could reduce cell proliferation and promoted cell apoptosis of RA-FLS via repressing SOX5, which may provide a new biological target for RA treatment.

MeSH terms

  • 3' Untranslated Regions
  • Antagomirs / metabolism
  • Apoptosis
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology*
  • Base Sequence
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • G1 Phase Cell Cycle Checkpoints
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • SOXD Transcription Factors / chemistry
  • SOXD Transcription Factors / genetics
  • SOXD Transcription Factors / metabolism*
  • Sequence Alignment
  • Synoviocytes / cytology
  • Synoviocytes / metabolism
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • MIRN212 microRNA, human
  • MicroRNAs
  • SOX5 protein, human
  • SOXD Transcription Factors