RNF8-mediated regulation of Akt promotes lung cancer cell survival and resistance to DNA damage
Yongjie Xu, Yumeng Hu, Tao Xu, Kaowen Yan, Ting Zhang, Qin Li, Fen Chang, Xueyuan Guo, Jingyu Peng, Mo Li, Min Zhao, Hongying Zhen, Luzheng Xu, Duo Zheng, Li Li, Genze Shao
Abstract
Despite the tremendous success of targeted and conventional therapies for lung cancer, therapeutic resistance is a common and major clinical challenge. RNF8 is a ubiquitin E3 ligase that plays essential roles in the DNA damage response; however, its role in the pathogenesis of lung cancer is unclear. Here, we report that RNF8 is overexpressed in lung cancer and positively correlates with the expression of p-Akt and poor survival of patients with non-small-cell lung cancer. In addition, we identify RNF8 as the E3 ligase for regulating the activation of Akt by K63-linked ubiquitination under physiological and genotoxic conditions, which leads to lung cancer cell proliferation and resistance to chemotherapy. Together, our study suggests that RNF8 could be a very promising target in precision medicine for lung cancer.