MicroRNA-29a inhibits proliferation and induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes by repressing STAT3

Biomed Pharmacother. 2017 Dec;96:173-181. doi: 10.1016/j.biopha.2017.09.120. Epub 2017 Oct 4.

Abstract

Rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) with aberrant expression of microRNA (miRNA) have been reported to be involved in the initiation, progression, and perpetuation of rheumatoid arthritis (RA). In this study, we explored the biological function and underlying mechanism of microRNA-29a (miR-29a) in cultured RA-FLS from RA patients. The expression of miR-29a in serum, synovial tissues, and FLS from RA patients and health donors was detected by real-time quantitative RT-PCR (qRT-PCR). The effects of miR-29a on cell proliferation, apoptosis, and inflammatory cytokine levels in RA-FLS were also determined using Counting Assay Kit-8 (CCK-8), flow cytometry, and enzyme-linked immunosorbent assay (ELISA) respectively. Luciferase reporter assay was carried out to identify the target genes of miR-29a. We observed that expression of miR-29a was markedly downregulated in serum, synovial tissues and FLS of RA patients. miR-29a overexpression in RA-FLS significantly inhibited proliferation, promoted apoptosis, and suppressed expression of inflammatory cytokines. Signal transducer and activator of transcription 3 (STAT3) was identified to be a direct target of miR-29a in RA-FLS. miR-29a overexpression suppressed the expression of STAT3, as well as phosphorylated STAT3(p-STAT3) and its downstream targets protein (Cyclin D1 and Bcl-2). In addition, the levels of miR-29a were inversely correlated with that of STAT3 in synovial tissues. Rescue experiments showed that overexpression of STAT3 effectively reversed the effect of miR-29a on proliferation and apoptosis in RA-FLS. These data indicate that miR-29a inhibits proliferation and induces apoptosis in RA-FLS by targeting STAT3, suggesting that promoting miR-29a expression may yield therapeutic benefits in the treatment of RA.

Keywords: Apoptosis; Proliferation; Rheumatoid arthritis; STAT3; miR-29a.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / physiology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Cell Proliferation / physiology*
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Male
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / biosynthesis*
  • Synoviocytes / metabolism*
  • Synoviocytes / pathology

Substances

  • MIRN29 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human