Circular RNA hsa_circ_0000175 Serves as a Potential Biomarker for Rheumatoid Arthritis via miR-31-5p/GSDME Axis.

Rheumatoid arthritis (RA) is a common inflammatory autoimmune disease characterized by synovial inflammation and joint damage. Previous studies have shown that pyroptosis plays an important role in the pathogenesis of RA. In this study, the effects of circular RNA hsa_circ0000175 on pyroptosis and inflammation of RA were evaluated. Serum levels of circ_0000175 and miR-31-5p were determined by RT-qPCR, and the correlation between them was evaluated by Spearman correlation analysis. Fibroblast-like synoviocytes (FLSs) were extracted and prepared for in vitro study. The subcellular localization of circ_0000175 was detected by FISH assay. Pyroptosis and inflammatory cytokines interleukin (IL)-1ß, IL-18 and IL-6 were measured by flow cytometry and ELISA, respectively. RNA pull-down and luciferase reporter assays verified the interaction between circ_0000175 and miR-31-5p. Western blot was used to detect the differential expression of pyroptosis-related factors (GSDME-N, GSDMD-N, cleaved caspase-1 and cleaved caspase-3). Circ_0000175 level was increased but miR-31-5p expression was decreased in PBMCs of RA patients and LPS/ATP-treated FLSs, companied with negative correlation. Moreover, miR-31-5p was a target of circ_0000175 in RA-FLSs. Silencing of circ_0000175 or overexpression of miR-31-5p significantly alleviated LPS/ATP-induced pyroptosis in FLSs through both caspase-1/GSDMD and caspase-3/GSDME pathways. Additionally, GSDME was identified as the target of miR-31-5p. The inhibitory effects of circ_0000175 depletion on pyroptosis and inflammation in RA-FLSs treated with LPS/ATP were strengthened by GSDME knockdown. Circ_0000175 can induce pyroptosis and trigger inflammatory response during the occurrence of RA through the miR-31-5p/GSDME axis, which provides a novel therapeutic target for RA treatment.

Long non-coding RNA TSPEAR Antisense RNA 2 is downregulated in rheumatoid arthritis and inhibits the apoptosis of fibroblast-like synoviocytes by downregulating microRNA-212-3p (miR-212-3p).

Long non-coding RNA (lncRNA) TSPEAR-AS2 (TSPEAR Antisense RNA 2) participates in many human diseases, while its roles in rheumatoid arthritis (RA) are unknown. Plasma expression levels of TSPEAR-AS2 and microRNA (miR)-212-3p in both RA patients and healthy controls were measured by RT-qPCR. Diagnostic potentials of plasma TSPEAR-AS2 and miR-212-3p were assessed by ROC curve analysis. Normalized expression levels of TSPEAR-AS2 and miR-212-3p were subjected to Pearson's correlation coefficient to evaluate their corrections. TSPEAR-AS2 was significantly downregulated in RA patients, while plasma expression levels of miR-212-3p were significantly increased in RA patients. The expression of TSPEAR-AS2 and miR-212-3p showed promising diagnostic value for RA. Plasma expression levels of TSPEAR-AS2 and miR-212-3p were significantly and inversely correlated in RA patients but not in healthy controls. Besides, overexpression of TSPEAR-AS2 decreased the apoptosis of RA HFLSs, while miR-212-3p increased cell apoptosis. In addition, miR-212-3p attenuated the effects of overexpression of TSPEAR-AS2. Overexpression of TSPEAR-AS2 decreased the expression levels of miR-212-3p in HFLS, while overexpression of miR-212-3p did not affect the expression of TSPEAR-AS2. In conclusion, TSPEAR-AS2 is downregulated in RA and its overexpression can decrease the apoptosis of RA HFLSs by downregulating miR-212-3p.