Circ_0002984 promotes proliferation, migration and inflammatory cytokine secretion and inhibits apoptosis of rheumatoid arthritis fibroblast-like synoviocytes by inducing PCSK6 through miR-543.

Abstract

Rheumatoid arthritis (RA) is inflammatory arthritic disease, and circular RNA is involved in RA development. The aim of the present work is to analyze the role of circ_0002984 in the process of RA fibroblast-like synoviocytes (RAFLSs) and the underlying mechanism. Circ_0002984, miR-543, and proprotein convertase subtilisin/kexin type 6 (PCSK6) expression levels were analyzed by quantitative real-time polymerase chain reaction or western blotting. Cell proliferation, migration, inflammatory response, and apoptosis were investigated through 5-Ethynyl-2'-deoxyuridine assay, wound-healing assay, enzyme-linked immunosorbent assay, and flow cytometry analysis. Dual-luciferase reporter assay and RNA immunoprecipitation assay were performed to assess the binding relationship. Circ_0002984 and PCSK6 expression were increased, while miR-543 expression was decreased in the synovial tissues of RA patients and RAFLSs. Circ_0002984 introduction facilitated RAFLS cell proliferation, migration and inflammatory response and repressed apoptosis, but circ_0002984 knockdown had an opposite role. Circ_0002984 targeted miR-543, and PCSK6 was targeted by miR-543. MiR-543 downregulation or PCSK6 overexpression restored the effects of circ_0002984 interference on RAFLS phenotypes. Circ_0002984 promoted RAFLS proliferation, migration and inflammatory cytokine secretion and inhibited apoptosis by binding to miR-543 to induce PCSK6 production, providing a potential target for RA therapy.