OBJECTIVE: To investigate the role of early growth response 1 (EGR1) in the progression of endometrial cancer (EC) and to elucidate the molecular mechanism by which EGR1 regulates ferroptosis, with a focus on NADPH oxidase 4 (NOX4) as a downstream mediator. METHODS: , MDA, GSH, and lipid ROS) and related proteins (GPX4, SLC7A11, and IREB2) were measured. The ferroptosis inhibitor Fer-1 was used for rescue experiments. Gene and protein expression were analyzed via RT-qPCR, western blotting, and immunohistochemistry. The transcriptional regulation of NOX4 by EGR1 was validated using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: promoter and increased its transcription, leading to increased ROS production and thereby facilitating ferroptosis. CONCLUSION: EGR1 inhibits the progression of EC at least in part through transcriptionally activating NOX4, which promotes ROS accumulation and contributes to ferroptosis induction. This study provides a theoretical basis for targeting EGR1 as a potential therapeutic strategy for treating EC.
Liu et al. (Tue,) studied this question.