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Circular RNAs (circRNAs) have been shown to play an important role in rheumatoid arthritis (RA) progression. This study aims to explore the role and mechanism of circ_0003972 in RA progression. Quantitative real-time PCR was used to determine gene expression. The proliferation and apoptosis of human RA fibroblast-like synovial (HFLS-RA) cells were measured using cell counting kit 8 assay, EdU staining and flow cytometry. Western blot analysis was performed to measure protein expression, and ELISA assay was used to examine the concentrations of inflammation factors. The interaction between miR-654-5p and circ_0003972 or FZD4 was confirmed by dual-luciferase reporter assay and RIP assay. Circ_0003972 was highly expressed in RA patients and HFLS-RA cells. Circ_0003972 knockdown inhibited the proliferation, inflammation, while promoted the apoptosis of TNFα-induced HFLS-RA cells. MiR-654-5p was downregulated in RA patients and HFLS-RA cells, and it could be sponged by circ_0003972. MiR-654-5p inhibitor reversed the effect of circ_0003972 silencing on the proliferation, inflammation, and apoptosis of TNFα-induced HFLS-RA cells. Frizzled-4 (FZD4) could be targeted by miR-654-5p, and its expression was positively regulated by circ_0003972. Furthermore, FZD4 overexpression also reversed the effects of miR-654-5p on proliferation, inflammation and apoptosis in TNFα-induced HFLS-RA cells. Our data suggested that circ_0003972 might promote the proliferation and inflammation of HFLS-RA cells to accelerate RA progression via regulating miR-654-5p/FZD4.

immunological investigations

Circ_0003972 Promotes the Proliferation and Inflammation of Fibroblast-like Synovial Cells in Rheumatoid Arthritis through Regulation of the miR-654-5p/FZD4 Axis