Cellular senescence-associated gene IFI16 promotes HMOX1-dependent evasion of ferroptosis and radioresistance in glioblastoma.

ABSTRACT: Glioblastoma multiforme (GBM) remains a therapeutic challenge due to its aggressive nature and recurrence. This study establishes a radioresistant GBM cell model through repeated irradiation and observes a cellular senescence-like phenotype in these cells. Comprehensive genomic and transcriptomic analyses identify IFI16 as a central regulator of this phenotype and contributes to radioresistance. IFI16 activates HMOX1 transcription thereby attenuating ferroptosis by reducing lipid peroxidation, ROS production, and intracellular Fe²⁺ content following irradiation. Furthermore, IFI16 interacts with the transcription factors JUND and SP1 through its pyrin domain, robustly facilitating HMOX1 expression, further inhibiting ferroptosis and enhancing radioresistance in GBM. Notably, gly

SUBMITTER: Zhou Y 

PROVIDER: S-EPMC11785807 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature