Identification of FADS2 as a Contributor of Ferroptosis Escape in Bladder Cancer.

Ferroptosis is an iron-dependent form of regulated cell death. Previous research indicates that inducing ferroptosis holds significant promise in cancer therapy, particularly for patients who have failed traditional treatments. However, the presence of a ferroptosis escape mechanism in bladder cancer remains unclear, and the therapeutic potential of ferroptosis induction in this context requires further exploration. In this study, bioinformatics analyses and immunohistochemical staining revealed that FADS2 is aberrantly overexpressed in bladder cancer, with its high expression correlating with poor prognosis. Both in vivo and in vitro experiments, including CCK-8 assays, lipid peroxidation assays, iron measurements and ferroptosis-related gene analyses, demonstrated that silencing FADS2 can trigger ferroptosis in bladder cancer cells. Mechanistically, inhibition of the mTOR pathway and SREBP activity was found to reduce FADS2 expression and promote ferroptosis in bladder cancer. In conclusion, this study identifies a critical gene involved in ferroptosis escape in bladder cancer and suggests that FADS2 could serve as a novel prognostic marker and therapeutic target.