IGF2BP3 Knockdown Induces Ferroptosis by Inhibiting Autophagy-Mediated EMC2 Degradation in Ovarian Cancer

Recent studies have increasingly demonstrated that chemoresistance in ovarian cancer primarily stems from resistance to oxidative stress and ferroptosis. Ferroptosis, a non-apoptotic form of cell death dependent on intracellular iron and marked by the buildup of lipid reactive oxygen species (ROS), has shown enhanced effectiveness in triggering cell death in ovarian cancer cells. Thus, this study aimed to explore the potential of gene knockdown associated with ferroptosis as an innovative therapeutic strategy against ovarian cancer. Up-regulated genes were identified using a gene bank, and their expression levels were validated through Western blotting (WB) and quantitative PCR (qPCR). Levels of MDA, Fe²⁺, GSH, ROS, SQSTM1, LC3-I and LC3-II in ovarian cancer cells treated with sorafenib and subjected to gene knockout were assessed using specific kits. Expression levels of proteins related to ferroptosis were analyzed by WB. Tumor size, volume, ferroptosis and autophagy in ovarian cancer tumor tissues were also examined. IGF2BP3 was elevated in human ovarian cancer and decreased during ferroptosis induced by sorafenib in human ovarian cancer cells. IGF2BP3 knockdown inhibited ovarian cancer cell function and promoted ferroptosis, in addition to autophagy-mediated EMC2 degradation. IGF2BP3 knockdown increased ovarian cancer sensitivity to sorafenib. This study confirmed that IGF2BP3 knockdown inhibited ovarian cancer cell malignancy, promoted ferroptosis and inhibited autophagy-mediated EMC2 degradation, and verified that IGF2BP3 knockdown increased the sensitivity to sorafenib in ovarian cancer mice.