Yu, Y.; Deng, H.; Song, P.; Liu, Y.; Qiu, Q.; Zhang, M.

Radiotherapy has significantly improved survival outcomes in glioblastoma (GBM) patients, particularly when combined with tumor resection and temozolomide chemotherapy. However, radioresistance remains a major obstacle, limiting further advances in prognosis and potential cure. DEPDC1, a gene implicated in various malignant phenotypes, has not yet been investigated for its role in GBM radioresistance, despite suggestive evidence from previous studies. In this study, analysis of the cancer database and GBM tissue microarrays revealed that DEPDC1 expression is significantly elevated in GBM tissues compared to normal brain tissues. Using GBM cell lines with DEPDC1 knockdown, we observed markedly reduced proliferation and motility. Notably, DEPDC1 downregulation significantly enhanced radiosensitivity, as demonstrated by increased radiation-induced apoptosis, G2/M phase arrest, DNA damage, and impaired DNA repair post-radiation, resulting in lower survival rates in clonogenic assays. Mechanistically, these effects may be mediated through DEPDC1-driven upregulation of NF-{kappa}B, supported by tumor sample analysis from our xenograft mouse model. Collectively, our findings suggest that DEPDC1 is not only involved in GBM malignancy but also represents a promising therapeutic target for overcoming radioresistance and developing effective radiosensitizers.