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

Abstract

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 α (TNF-α)-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-α-treated RA-FLSs. Circ_0088036 interference largely reversed TNF-α-induced proliferation and inflammation in RA-FLSs. The interaction between circ_0088036 and miR-326 was verified, and miR-326 silencing largely reversed circ_0088036 knockdown-mediated effects in TNF-α-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-α-treated RA-FLSs. Circ_0088036 could up-regulate FZD4 by sponging miR-326 in RA-FLSs.

Conclusion

Circ_0088036 contributed to TNF-α-induced RA progression partly by targeting miR-326/FZD4 signalling.

Keywords:

• Rheumatoid arthritis
• TNF-α
• circ_0088036
• miR-326
• FZD4

Ethical approval

The studies involving human participants were reviewed and approved by ethical committee of Affiliated Hospital of Chengde Medical College.

Consent to participate

All patients had signed written informed consents.

Disclosure statement

The authors declare that they have no financial conflicts of interest.

Data availability statements

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.