Cancer associated fibroblast secreted miR-432-5p targets CHAC1 to inhibit ferroptosis and promote acquired chemoresistance in prostate cancer

Abstract

Abstract Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Cancer-associated fibroblasts (CAF) are an integral part of the tumor microenvironment and play an important role in tumorigenesis. To understand the potential mechanisms of chemoresistance in prostate cancer, we investigated the role of CAF-derived exosomes in ferroptosis. CAF exosomes inhibited erastin-induced lipid reactive oxygen species (ROS) accumulation in prostate cancer cells and reduced erastin induced damage to mitochondria, thereby inhibiting ferroptosis in prostate cancer cells. miR-432-5p inhibits ferroptosis in prostate cancer cells by targeting CHAC1 to reduce glutathione (GSH) depletion in cells thereby inhibiting ferroptosis. miR-432-5p inhibition enhances the drug sensitivity of PC (prostate cancer) cells in vivo. We found that exosomal miR-432-5p secreted by CAF targets CHAC1 via the ferroptosis pathway, thereby promoting chemoresistance in PC. This study provides a new approach for docetaxel resistance.