PTBP1 functions as a suppressor of ferroptosis in endometrial carcinoma cells by stabilizing SLC7A11 mRNA

The RNA-binding protein PTBP1 facilitates tumor progression in various cancers by interacting with mRNAs of key oncogenes and tumor suppressors, thereby regulating their mRNA stability, alternative splicing, and protein translation. In this study, PTBP1 knockdown notably inhibited both in vitro cell viability and in vivo tumor growth in endometrial cancer cells. Elevated PTBP1 protein levels were also observed in endometrial cancer tissues compared to normal endometrial tissues. Transcriptomic sequencing revealed that PTBP1 depletion might impact lipid metabolism and ferroptosis in endometrial cancer cells. Through measurements of intracellular ROS, GSH, MDA, and Fe2+ levels, along with the expression of ferroptosis-related genes (ACSL4, NOX1, GPX4, and HSP27), it was demonstrated that PTBP1 knockdown significantly enhances ferroptosis in endometrial cancer cells. Mechanistic studies further indicated that PTBP1 binds to the 5' UTR of SLC7A11 mRNA, stabilizing it and preserving SLC7A11 protein expression, thus inhibiting ferroptosis. This study elucidates the molecular mechanism by which PTBP1 promotes endometrial cancer progression through suppression of ferroptosis, suggesting that PTBP1 may be a promising therapeutic target for endometrial cancer.