Akt/mTOR pathway-mediated CCNA1 regulation of radiotherapy resistance in nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC), as a cancer type highly sensitive to radiotherapy, has radiation therapy as the preferred clinical treatment strategy. However, acquired radioresistance poses a significant challenge to the overall therapeutic efficacy for NPC patients. METHODS: In this study, we established two radioresistant NPC cell lines, CNE2-IR and HONE1-IR. RESULTS: RNA sequencing analysis revealed that CCNA1 was upregulated in both radioresistant NPC cell lines. Downregulation of CCNA1 enhanced the radiosensitivity of these two radioresistant NPC cell lines. Further research found that CCNA1 expression was induced and upregulated during radiotherapy and was associated with poor prognosis in NPC patients. Through in-depth mechanistic studies, we confirmed that CCNA1 may influence radiosensitivity through ROS antioxidant stress and anti-apoptotic signaling. High expression of CCNA1 enhanced NPC cell viability and inhibited apoptosis, while downregulating CCNA1 improved the radiosensitivity of NPC cells. The mechanism of radiosensitization was primarily mediated by the AKT/mTOR pathway. CONCLUSIONS: These findings suggest that CCNA1 could serve as a potential predictive biomarker for radiosensitivity in NPC patients, providing new insights for developing personalized comprehensive chemoradiotherapy strategies for NPC patients.