Dioscin alleviates the dysfunction of fibroblast-like synoviocytes by circ_0008267/miR-942-5p/FKBP5 axis during rheumatoid arthritis.

Abstract

Dioscin is a natural, bioactive steroid saponin that has the antiarthritic activity. Circular RNAs (circRNAs) are stable noncoding RNAs involving in the pathogenesis of rheumatoid arthritis (RA). Here, this study aimed to probe the role and mechanism of dioscin and circ_0008267 in RA progression. Cell proliferation, apoptosis, invasive, and migratory abilities, as well as inflammatory response were evaluated by CCK-8 assay, EdU assay, flow cytometery, transwell assay, wound healing assay, and ELISA analysis, respectively. Levels of genes and protein were tested by qRT-PCR and western blotting. The interaction between miR-942-5p and circ_0008267 or FK506-binding protein 5 (FKBP5) was confirmed using dual-luciferase reporter and RNA pull-down assays. Dioscin treatment was demonstrated to suppress RA-FLS proliferation, invasion, migration, and inflammatory response, but induced cell apoptosis. Circ_0008267 is a stable circRNA, and was increased in RA samples. Moreover, its expression was reduced by dioscin in RA-FLS, overexpression of circ_0008267 reversed the effects of dioscin on RA-FLS. Mechanistically, circ_0008267 acted as a sponge for miR-942-5p, which targeted FKBP5. Dioscin reduced FKBP5 expression, but elevated miR-942-5p level in RA-FLS. MiR-942-5p inhibition or FKBP5 upregulation abolished the inhibitory effects of dioscin on RA-FLS dysfunction. Moreover, circ_0008267 deficiency impaired RA-FLS proliferation, invasion, migration, and inflammation through regulating FKBP5. Dioscin suppressed the proliferation, invasion, migration, and inflammatory response in RA-FLS via circ_0008267/miR-942-5p/FKBP5 axis, providing new insights for RA prevention.