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

CircNOP14 通过抑制 Ku70 依赖的 DNA 损伤修复来增加肝细胞癌的放射敏感性

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作者:Letao Lin, Pan Hu, Ma Luo, Xi Chen, Meigui Xiao, Zhihui Zhong, Sheng Peng, Guanyu Chen, Guang Yang, Fujun Zhang, Yanling Zhang

Abstract

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.

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