Circ_0088036 mediated progression and inflammation in fibroblast-like synoviocytes of rheumatoid arthritis by miR-1263/REL-activated NF-?B pathway

Background: Rheumatoid arthritis (RA) is a common joint disease with abnormal development of human fibroblast-like synoviocytes (HFLS). Circular RNAs (circRNAs) have essential regulation in the disease progression, and this study was to explore the regulatory mechanism of circ_0088036 in RA. Methods: RNA expression analysis was performed through reverse transcription-quantitative polymerase chain reaction assay. Cell experiments were conducted by Cell Counting Kit-8 assay for cell viability, EdU (5-ethynyl-2'- deoxyuridine) assay for proliferation and flow cytometry for cell cycle or apoptosis. The protein detection was conducted using western blot. Enzyme-linked immunosorbent assay (ELISA) was used to examine the inflammatory cytokines. The binding identification was carried out through dual-luciferase reporter assay, RNA immunoprecipitation assay and pull-down assay. Results: The level of circ_0088036 RNA was significantly upregulated in sera and in HFLS cells of RA patients. Targeted silencing of circ_0088036 restrained proliferation, cell cycle progression and inflammatory reaction through promoted the apoptosis of HFLS-RA cells via inhibiting the NF-kappa B pathway. The miR-1263 was identified as a target of circ_0088036. MiR-1263 was found to be down-regulated in sera and in HFLS cells of RA patients. The regulatory effects of circ_0088036 on HFLS-RA cells were attributed to inhibit the miR-1263 level. REL is a susceptibility locus for certain autoimmune diseases. MiR-1263 directly targeted REL, which was discovered to be elevated in sera and HFLS cells of RA patients, and circ_0088036 interacted with miR-1263 to affect REL expression. Functionally, overexpression of miR-1263 suppressed the development of HFLS-RA by blocking the NF-kappa B pathway, and this phenomenon was reversed by the upregulation of REL. Conclusion: These findings suggested that circ_0088036/miR-1263/REL/NF-kappa B pathway was involved in the functional development of HFLS-RA cells, indicating a novel molecular network in RA progression in vitro.

Automated summary

This study reveals the important role of circ_0088036/miR-1263/REL/NF-kappa B pathway in the functional development of HFLS-RA cells, indicating a novel molecular network in the progression of RA in vitro.