FERMT1 suppresses the ferroptosis of glioma cells by interacting with MBOAT2.

Abstract

Gliomas, particularly high-grade glioblastomas, are highly aggressive malignancies with limited treatment options and poor prognosis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a promising therapeutic target in cancer. However, the mechanisms regulating ferroptosis in glioma remain poorly understood. In this study, we identify FERMT1 as a key suppressor of ferroptosis in glioma cells. Using gain and loss-of-function experiments, we demonstrate that FERMT1 overexpression protects glioma cells from erastin-induced ferroptosis, while FERMT1 deficiency sensitizes cells to ferroptotic cell death. Treatment with the ferroptosis inhibitor ferrostatin-1 mitigates the effects of FERMT1 deficiency, underscoring the importance of ferroptosis suppression in FERMT1-mediated oncogenesis. Mechanistically, FERMT1 interacts with MBOAT2 to suppress ferroptosis. Depletion of MBOAT2 abolishes the anti-ferroptotic effects of FERMT1, whereas MBOAT2 overexpression rescues ferroptosis in FERMT1-deficient cells. Collectively, our findings reveal a previously unrecognized FERMT1-MBOAT2 axis that regulates ferroptosis in glioma cells and provide new insights into the molecular mechanisms underlying glioma progression. Targeting this axis may offer a novel therapeutic strategy for inducing ferroptosis and improving treatment outcomes in glioma.