Abstract

Several studies have suggested that fibroblast-like synoviocytes (FLSs) 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. The levels of miR-6089 were detected to be significantly lower in the synovial tissues and FLSs of RA than in the healthy synovial tissues and FLSs. The miR-6089 up-regulation in RA-FLSs significantly inhibited the proliferation and promoted cell apoptosis accompany with an increase protein expression of cleaved-Caspase-3, -8 and -9. Furthermore, CCR4 was determined to target miR-6089 directly, and its expression was significantly increased in the synovial tissues of RA than in the healthy synovial tissues. The overexpression of CCR4 reversed the effect of miR-6089 on proliferation and apoptosis in RA-FLSs effectively. In conclusion, our study suggests that the miR-6089 may be a potential target for prevention and treatment of RA.

摘要

几项研究表明，成纤维细胞样滑膜细胞 (FLS) 和 miRNA 与类风湿性关节炎 (RA) 的发病机制有关。本研究旨在评估 miR-6089 在调节 RA-FLS 中的功能。检测到 RA 的滑膜组织和 FLSs 中 miR-6089 的水平显着低于健康滑膜组织和 FLSs。RA-FLSs 中 miR-6089 的上调显着抑制增殖并促进细胞凋亡，同时增加了 cleaved-Caspase-3、-8 和 -9 的蛋白表达。此外，CCR4 被确定直接靶向 miR-6089，其在 RA 滑膜组织中的表达明显高于在健康滑膜组织中的表达。CCR4的过表达有效地逆转了miR-6089对RA-FLSs增殖和凋亡的影响。总之，我们的研究表明 miR-6089 可能是预防和治疗 RA 的潜在靶点。