Notably, GPX4 restoration significantly counteracted with the enhancement of DHA-induced ROS, MDA and lipid ROS production as well as cell death rate by HSPA5 silencing in both U251 and U373 cells (Fig. 7d and Additional file 1: Figure S9), suggesting that GPX4 mediated the anti-ferroptotic effects of HSPA5 against DHA in glioma cells. This evidence concerns the gene GPX4 and central nervous system cancer.