RPA1 downregulation enhances nasopharyngeal cancer radiosensitivity via blocking RAD51 to the DNA damage site

Area of Science:

• Oncology
• Molecular Biology
• Radiation Oncology

Background:

• Nasopharyngeal cancer (NPC) exhibits high local recurrence due to resistance to ionizing radiation (IR).
• Replication protein A1 (RPA1) is crucial for homologous repair (HR) of DNA double-strand breaks (DDBs).
• Limited research exists on RPA1's role in NPC radiosensitivity.

Purpose of the Study:

• To investigate the role of RPA1 in predicting radiosensitivity in NPC.
• To explore RPA1's impact on DNA repair, cell proliferation, and tumor growth post-irradiation.

Main Methods:

• Immunohistochemistry evaluated RPA1 protein expression in 182 NPC patients.
• Univariate and multivariate analyses assessed RPA1's correlation with clinicopathological features.
• RPA1 was silenced in CNE-2R cells to assess radiosensitivity, proliferation, DNA repair, and cell cycle.
• Xenograft models were used to evaluate RPA1's effect on tumor growth after IR.

Main Results:

• RPA1 was overexpressed in NPC patients with non-complete response (nCR), predicting radiosensitivity.
• Silencing RPA1 increased radiosensitivity, blocked DNA repair, impaired proliferation, and induced G2/M arrest in CNE-2R cells.
• Silencing RPA1 combined with irradiation significantly retarded tumor growth in xenograft models.

Conclusions:

• RPA1 is frequently overexpressed in NPC patients with nCR.
• Silencing RPA1 enhances NPC cell radiosensitivity.
• RPA1 is a potential biomarker for predicting radiosensitivity in NPC.