STRA6-mediated ferroptosis and its potential association with antioxidant stress pathways in glioblastoma

Glioma is the most common malignant tumor of the central nervous system, but the role of stimulated by retinoic acid 6 (STRA6) in its progression remains unclear. We established STRA6-knockdown and STRA6-overexpressing glioma cell lines to investigate their effects on malignant behavior and ferroptosis and validated the findings in a subcutaneous allograft model. STRA6 was upregulated in glioma tissues and associated with poor overall survival. Silencing STRA6 inhibited glioma cell proliferation, migration, and invasion; increased Fe 2+ and malondialdehyde levels; reduced glutathione levels; and induced ferroptosis, whereas STRA6 overexpression exerted opposite effects. Ferrostatin-1 and deferoxamine attenuated ferroptosis induced by STRA6 knockdown, while Erastin reversed the effects of STRA6 overexpression. Collectively, these findings suggest that STRA6 promotes glioma progression by suppressing ferroptosis through the regulation of cellular antioxidant stress-related pathways, highlighting STRA6 as a potential therapeutic target for glioma.