Abstract

Background

Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are implicated in the pathogenesis of RA. This study investigated the role of lncRNA ZNF667-AS1 in RA progression.

Methods

Synovial tissues and fibroblast-like synoviocytes (FLSs) were obtained from patients with RA. Gene expression was measured using RT-qPCR. Chondrocytes were treated with lipopolysaccharide (LPS) to establish in vitro models of OA. Cell counting kit-8 (CCK-8), western blot, and enzyme-linked immunosorbent assay (ELISA) were used to examine the proliferation and inflammatory cytokine production in chondrocytes. Animal models of OA were established in SD rats. Peripheral blood mononuclear cells (PBMCs) were isolated from the OA rats. Flow cytometry was used to measure the changes of the inflammatory T-helper cell 17 (Th17) cells. The relationship between ZNF667-AS1 and miR-523-3p was verified by luciferase reporter assay.

Results

ZNF667-AS1 was downregulated in RA-FLSs and LPS-stimulated chondrocytes. ZNF667-AS1 overexpression significantly promoted cell proliferation and inhibited the production of IL-6, IL-17 and TNF-α in LPS-stimulated chondrocytes. Additionally, ZNF667-AS1 overexpression reduced the generation of CD4 + IL-17+ cells. In mechanism, ZNF667-AS1 acted a sponge for miR-523-3p. MiR-523-3p overexpression reversed the ZNF667-AS1-mediated regulation of cell proliferation and inflammation. Furthermore, miR-523-3p overexpression abolished the inhibitory effects of ZNF667-AS1 on the JAK/STAT signalling activation.

Conclusion

ZNF667-AS1 exerts protective effects during RA development by sponging miR-523-3p and inactivating the JAK/STAT signalling.

中文翻译：

---

LncRNA ZNF667-AS1 通过海绵化 miR-523-3p 和灭活 JAK/STAT 信号通路来缓解类风湿性关节炎

摘要

背景

类风湿性关节炎 (RA) 是一种自身免疫性疾病，它会损害滑膜导致慢性炎症。越来越多的证据表明，长链非编码 RNA (lncRNA) 与 RA 的发病机制有关。本研究调查了 lncRNA ZNF667-AS1 在 RA 进展中的作用。

方法

滑膜组织和成纤维细胞样滑膜细胞 (FLS) 来自 RA 患者。使用 RT-qPCR 测量基因表达。用脂多糖 (LPS) 处理软骨细胞以建立OA的体外模型。细胞计数试剂盒 8 (CCK-8)、蛋白质印迹和酶联免疫吸附试验 (ELISA) 用于检查软骨细胞中的增殖和炎性细胞因子的产生。在SD大鼠中建立OA动物模型。从 OA 大鼠中分离出外周血单个核细胞 (PBMC)。流式细胞仪用于测量炎性 T 辅助细胞 17 (Th17) 细胞的变化。ZNF667-AS1 和 miR-523-3p 之间的关系通过荧光素酶报告基因测定得到验证。

结果

ZNF667-AS1 在 RA-FLS 和 LPS 刺激的软骨细胞中下调。ZNF667-AS1 过表达显着促进细胞增殖并抑制 LPS 刺激的软骨细胞中 IL-6、IL-17 和 TNF-α 的产生。此外，ZNF667-AS1 过表达减少了 CD4 + IL-17 + 细胞的生成。在机制上，ZNF667-AS1 充当了 miR-523-3p 的海绵。MiR-523-3p 过表达逆转了 ZNF667-AS1 介导的细胞增殖和炎症调节。此外，miR-523-3p 过表达消除了 ZNF667-AS1 对 JAK/STAT 信号激活的抑制作用。

结论

ZNF667-AS1 通过海绵化 miR-523-3p 和灭活 JAK/STAT 信号传导在 RA 发展过程中发挥保护作用。