Downregulation of microRNA‑221 decreases migration and invasion in fibroblast‑like synoviocytes in rheumatoid arthritis.

Abstract

MicroRNAs (miRNAs/miRs) are a group of non-coding RNAs that regulate the activity of target mRNAs and cellular processes, and which have been implicated in the pathogenesis of autoimmune diseases. miR-221 is one of the miRNAs that regulate cell proliferation, invasion and apoptosis in tumors. However, the role of miR-221 in rheumatoid arthritis (RA) remains to be fully elucidated. Therefore, the present study was undertaken to identify the role of miR-221 in RA. The expression of miR-221 in serum and synovial tissues of patients with RA and healthy controls was confirmed by reverse transcription quantitative polymerase chain reaction analysis. The effects of miR-221 on pro-inflammatory cytokines and a chemokine were assessed by ELISA. The effects of miR-221 on cell apoptosis, migration and invasion in fibroblast-like synoviocytes (FLS) were also assessed in vitro. The results showed that miR-221 expression in serum and synovial tissues of patients with RA was higher than that in healthy controls. Downregulation of miR-221 significantly suppressed the expression of pro-inflammatory cytokines and the chemokine, and inhibited FLS cell migration and invasion via inhibiting vascular endothelial growth factor, matrix metalloproteinase (MMP)-3 and MMP-9 expression. In addition, downregulation of miR-221 significantly induced cell apoptosis and decreased survivin and X-linked inhibitor of apoptosis protein expression. These findings indicated that downregulation of miR-221 inhibited the expression of pro-inflammatory cytokines and the chemokine, suppressed FLS cell migration and invasion, and induced cell apoptosis. Therefore, miR-221 is likely to be implicated in RA pathogenesis via these mechanisms, and may be a target for the treatment of RA.