Circ_0088036 facilitates the proliferation and inflammation and inhibits the apoptosis of fibroblast-like synoviocytes through targeting miR-326/FZD4 axis in rheumatoid arthritis

Background: The function and pathological significance of circular RNAs (circRNAs) in autoimmune diseases, such as rheumatoid arthritis (RA), are barely known. Here, we explored the role of circ_0088036 in RA progression and its associated mechanism. Methods: The synovial lining layer tissues of RA patients and non-RA control patients were collected for clinical study in vivo, and tumour necrosis factor alpha (TNF-alpha)-induced RA-fibroblast-like synoviocytes (RA-FLSs) were used for the experiments in vitro. Cell proliferation was assessed by Cell Counting Kit 8 (CCK8) assay and flow cytometry. Cell apoptosis was analyzed by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the release of pro-inflammatory cytokines. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target interaction between microRNA-326 (miR-326) and circ_0088036 or frizzled class receptor 4 (FZD4). Results: Circ_0088036 expression was elevated in the synovial lining layer tissues of RA patients and TNF-alpha-treated RA-FLSs. Circ_0088036 interference largely reversed TNF-alpha-induced proliferation and inflammation in RA-FLSs. The interaction between circ_0088036 and miR-326 was verified, and miR-326 silencing largely reversed circ0088036 knockdown-mediated effects in TNF-alpha-treated RA-FLSs. MiR-326 bound to the 3' untranslated region (3'UTR) of FZD4 in RA-FLSs. FZD4 overexpression largely diminished miR-326 accumulation-mediated influences in TNF-alpha-treated RA-FLSs. Circ_0088036 could up-regulate FZD4 by sponging miR-326 in RA-FLSs. Conclusion: Circ_0088036 contributed to TNF-alpha-induced RA progression partly by targeting miR-326/FZD4 signalling.

Automated summary

The study investigates the role of circ_0088036 in the progression of rheumatoid arthritis (RA) by targeting the miR-326/FZD4 signaling pathway in synovial lining layer tissues and RA-fibroblast-like synoviocytes (RA-FLSs). The findings suggest that circ_0088036 contributes to TNF-alpha-induced RA progression by interfering with miR-326 and upregulating FZD4.