MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis

OBJECTIVE: STAT3 expression is elevated in the synovial tissue of patients with rheumatoid arthritis (RA). MiR-20a plays a role in mediating synovial inflammation in RA. Bioinformatics analysis has identified a binding site between miR-20 and the 3'-UTR of STAT3 mRNA. This study aimed to investigate the role of miR-20a in the regulation of STAT3 expression and synovial cell proliferation as well as apoptosis.

PATIENTS AND METHODS: Synovial tissues were collected from RA patients and osteoarthritis (OA) patients to measure miR-20a, STAT3, p-STAT3, and Ki-67 expressions. Fibroblast-like synoviocytes (FLS) were treated with IL-17 (10 ng/ml) and then Ki-67 expression and cell cycle were evaluated by flow cytometry. The targeting relationship between miR-20a and STAT3 was assessed by dual luciferase reporter gene assay. FLS cells were divided into five groups: miR-NC, miR-20a mimic, si-NC, si-STAT3, and miR-20a mimic + si-STAT3 groups.

RESULTS: In RA patients, significantly lower MiR-20a expression, and substantially higher STAT3, p-STAT3, and Ki-67 expression were found in the synovial tissues compared with those in OA patients. IL-17A treatment markedly promoted FLS cell proliferation, inhibited cell apoptosis, reduced miR-20a expression, as well as upregulated levels of STAT3, p-STAT3, and Bcl-2. MiR-20a played a regulatory function on the expression of STAT3. MiR-20a mimic and/or si-STAT3 transfection apparently downregulated STAT3, p-STAT3, and Bcl-2 expression, attenuated IL-17A-induced cell proliferation promotive and enhanced cell apoptosis in FLS cells.

CONCLUSIONS: The expression of miR-20a was reduced in synovial tissue of RA patients with the increased level of STAT3. Downregulation of miR-20a promoted the expression of STAT3, p-STAT3, and Bcl-2, facilitated FLS cell proliferation, reduced apoptosis and, thereby, played a critical role in RA.

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