MiRNA-6089 inhibits rheumatoid arthritis fibroblast-like synoviocytes proliferation and induces apoptosis by targeting CCR4

Abstract

Background: Growing data have indicated that fibroblast-like synoviocytes (FLS) and miRNAs are implicated in the pathogenesis of rheumatoid arthritis (RA). This study was aimed to evaluate the function of miR-6089 in the regulation of RA-FLSs. Methods: The expression of miR-6089 was measured by quantitative real time PCR (qRT-PCR). The RA-FLSs were transfected with si-CCR4 plasmids or miR-6089 mimic, and subjected to CCK-8 and flow cytometry to analyze proliferation and apoptosis. The concentrations of MMP-1, TNF-α and IL-6 in RA-FLSs supernatant were detected using ELISA. The protein expression of caspase-3, -8 and -9 was detected using western blot.Results: The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the synovial tissues and FLSs of healthy controls. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of caspase-3, -8 and -9. Furthermore, CCR4 was determined to directly target miR-6089, and its expression was significantly increased in the synovial tissues of RA than in the synovial tissues of healthy controls. Moreover, CCR4 overexpression effectively reversed the effect on proliferation and apoptosis induced by miR-6089 in RA-FLSs. Conclusion: Our results revealed that miR-6089 may be a potential target for RA prevention and therapy of RA.