Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.

据报道，环状 RNA_0004712 (circ_0004712) 在类风湿关节炎 (RA) 患者中上调。然而，其在 RA 病理学中的作用和机制仍有待阐明。通过逆转录-定量聚合酶链反应 (RT-qPCR) 和蛋白质印迹法测定 RNA 和蛋白质表达。通过 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 测定、5-ethynyl-20-deoxyuridine 测定、流式细胞术、划痕试验评估细胞活力、增殖、凋亡、迁移和炎症和酶联免疫吸附试验。microRNA-633 (miR-633) 和circ_0004712 或TNF 受体相关因子6 (TRAF6) 之间的目标相关性通过双荧光素酶报告基因测定和RNA 免疫沉淀测定验证。Circ_0004712 在 RA 滑膜组织和 RA 成纤维细胞样滑膜细胞 (RA-FLS) 中被上调。Circ_0004712 沉默抑制了 RA-FLS 的活力、增殖、迁移和炎症反应，并促进了细胞凋亡。miR-633 被证实是 circ_0004712 的直接靶标，miR-633 敲低逆转了 circ_0004712 沉默介导的对 RA-FLSs 功能障碍和炎症的保护作用。TRAF6 是 miR-633 的直接靶标，miR-633 过表达通过下调 TRAF6 抑制 RA-FLS 的侵袭性变化。Circ_0004712 可以通过在 RA-FLS 中海绵化 miR-633 来上调 TRAF6 表达。Circ_0004712 通过靶向 miR-633/TRAF6 轴干扰灭活核因子 (NF)-κB 信号。