Impact of KDM4C on the radiosensitivity of glioblastoma cells

To elucidate the role of lysine-specific demethylase 4 C (KDM4C), characterized by its upregulation in glioblastoma (GBM) cells following X-ray irradiation (IR), in GBM radiosensitivity. KDM4C overexpression in GBM cell lines U87 and U251 was investigated to determine its impact on radiosensitivity by assessing clonogenic survival, DNA damage responses, and apoptosis rates following X-ray IR. Transcriptional changes associated with KDM4C upregulation were also analyzed in U251 cells after IR exposure. Furthermore, U251-derived xenograft models were utilized to evaluate the effect of KDM4C on radiosensitivity in vivo. KDM4C overexpression in GBM cells U87 and U251 resulted in increased clonogenic survival rates, diminished DNA damage responses, and reduced apoptosis rates after IR exposure. Treatment with the KDM4C inhibitor SD70 effectively counteracted these effects. Upregulation of KDM4C induced substantial transcriptional remodeling in U251 cells following IR exposure. In vivo, KDM4C overexpression decreased IR-induced upregulation of Cleaved-Caspase 3 in U251-derived xenografts. These findings highlight the critical role of KDM4C in reducing GBM radiosensitivity, suggesting that a therapeutic strategy combining radiotherapy with KDM4C inhibition may provide a promising approach to enhance treatment outcomes in GBM.