AS-IV inhibits the progression of ovarian cancer by targeting the circ_0124787/miR-6875–3p/IL-1β axis
Astragaloside IV (AS-IV), a bioactive saponin from Astragalus membranaceus, demonstrates strong anti-tumor effects across various cancers by modulating circular RNAs (circRNAs). Utilizing gene microarray analysis, we identified circ_0124787 as the most abundantly expressed circRNA in ovarian carcinoma tissues. ELISA assays showed that the secretion of IL-1β was significantly increased in the supernatants of SKOV3 and ID8 ovarian cancer cell lines which overexpressing circ_0124787. As a pivotal pro-inflammatory cytokine, IL-1β enhances γδT17 cell proliferation and amplifies inflammatory signaling, which promotes the tumor progression. TargetScan predicted miR-6875-3p as a putative target of circ_0124787, and this prediction was validated by dual-luciferase reporter assays. Functional studies demonstrated that circ_0124787 acts as a competitive endogenous RNA (ceRNA) by sponging miR-6875-3p, thereby derepressing its downstream effector IL-1β. Critically, inhibition of miR-6875-3p completely abolished the anti-tumor efficacy of AS-IV, thereby establishing the indispensability of this circRNA-miRNA axis for its therapeutic activity. Our results describe a novel AS-IV/circ_0124787/miR-6875-3p/IL-1β pathway that can decrease the proportion of γδT17 cell to suppress ovarian cancer.