STEAP3 regulates ferroptosis through mitochondrial metabolic dysfunction to impact the malignant proliferation of ovarian cancer cells.

Background Six-Transmembrane Epithelial Antigen of the Prostate 3 (STEAP3), a ferroptosis-related protein, regulates ferroptosis and cell metabolism in multiple tumors; however, its mechanism in ovarian cancer (OC) remains unclear. Methods STEAP3 expression in OC cells (HO-8910PM, SKOV3, OVCAR3, A2780) and normal IOSE80 cells was detected by western blotting and qRT-PCR. OC cells with STEAP3 knockdown or overexpression were then constructed. CCK-8 and EdU assays were used to evaluate cell proliferation; transmission electron microscopy, MitoSOX, TMRE, and mitochondrial respiratory chain complex detection were used to assess mitochondrial metabolism; bioinformatics analyzed STEAP3’s association with mitochondrial metabolism and ferroptosis; reactive oxygen species (ROS) and ferroptosis-related proteins were used to detect STEAP3-ferroptosis links; and nude mouse subcutaneous xenograft models were used to test tumor growth. ResultsSTEAP3 knockdown inhibited the proliferation of OC cells, induced mitochondrial metabolic dysfunction, and promoted ferroptosis in OC cells; in contrast, STEAP3 overexpression exerted the opposite effects. Fer-1 partially reversed the inhibition of OC cell proliferation caused by STEAP3 knockdown, whereas Erastin partially reversed the pro-proliferative effect of OC cells induced by STEAP3 overexpression. In vitro experiments showed that STEAP3 knockdown and overexpression resulted in consistent changes in tumor cell proliferation phenotypes. ConclusionSTEAP3 regulates ferroptosis via mitochondrial metabolic dysfunction, affecting the malignant proliferation of OC cells.