CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA—hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC. •The study identifies circNOP14 as a novel circRNA, enhancing radiosensitivity in HCC.•It uncovers that circNOP14 achieves this effect through modulation of the Ku70-dependent DNA damage repair pathway.•This research pioneers circRNAs' influence on radiosensitivity in HCC cells undergoing 125I seed brachytherapy.•The findings suggest that circNOP14 holds promise as a potential prognostic biomarker and radiosensitive target.