Anti‐Apoptotic and Anti‐Oxidative Effects of DDX24 Through HO‐1 Transcriptional Regulation

DEAD‐box helicase 24 (DDX24) is a member of the DEAD‐box protein family, which is essential for various aspects of RNA metabolism. DDX24 has been reported to play a role in ribosome biogenesis, transcription, and mRNA stability. Previous studies have implicated the functions of DDX24 in innate immunity, vascular malformation, cell growth, and cancer progression. Here, we describe a novel function of DDX24 in regulating the oxidative stress response and protecting cells from apoptosis. Our research revealed that DDX24 specifically regulates the expression of the heme oxygenase‐1 ( HO‐1 ) gene, as determined by RNA sequencing analysis. HO‐1 is responsible for degrading heme into carbon monoxide (CO), biliverdin, and ferrous ion (Fe 2+ ), thereby exerting anti‐apoptotic and anti‐oxidative effects. We validated the regulation of HO‐1 by DDX24 in both DDX24‐depleted and DDX24‐overexpressing cells. Our findings indicate that DDX24 is involved in the induction of HO‐1 expression under oxidative stress conditions. Importantly, DDX24 regulates the transcription of HO‐1 instead of its mRNA stability, likely acting at the promoter and enhancer E1 region of the HO‐1 gene. Furthermore, DDX24 depletion in HEK293T cells inhibits cell viability. DDX24 exerts both anti‐apoptotic and anti‐oxidative effects during oxidative stress. These results suggest that DDX24 plays a crucial role in protecting cells from oxidative stress‐induced damage by regulating the transcription of HO‐1 .