MiR-613 inhibits proliferation and invasion and induces apoptosis of rheumatoid arthritis synovial fibroblasts by direct down-regulation of DKK1

Abstract

Abstract Background This study aimed to investigate the effects of miR-613 on the proliferation, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). Methods Synovial tissue samples were collected from 20 rheumatoid arthritis (RA) patients and 10 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-613 and DKK1 expression in both synovial tissues and cells was detected using quantitative real-time PCR (qRT-PCR). Dual luciferase reporter gene assay was employed to evaluate the effect of miR-613 on the luciferase activity of DKK1. Then RASFs were transfected with miR-613 mimics, si-DKK1 and pcDNA-DKK1. Changes in cellular proliferation, invasion and apoptosis were detected through BrdU assay, Transwell invasion assay and flow cytometry analysis, respectively. Results MiR-613 was significantly down-regulated in RA tissues and RASFs compared to normal tissues and cells, whereas DKK1 was up-regulated in RA tissues and RASFs. Dual luciferase reporter gene assay showed that miR-613 could specifically bind to the 3′UTR of DKK1 and significantly inhibit the luciferase activity. Moreover, miR-613 significantly reduced the expression of DKK1. Overexpression of miR-613 or knockdown of DKK1 suppressed proliferation and invasion of RASFs, and induced RASF apoptosis. The reverse results were observed when DKK1 was up-regulated in miR-613-overexpressing RASFs. Conclusions MiR-613 can inhibit proliferation and invasion and induce apoptosis of RASFs by directly targeting DKK1 expression.

Keywords

• Rheumatoid arthritis
• MicroRNA-613
• Rheumatoid arthritis synovial fibroblasts
• DKK1
• Proliferation
• Apoptosis