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 identified the role of RNF8 in the carcinogenesis and chemoresistance of lung cancer. RNF8 is overexpressed in lung cancer, and positively correlates with the expression of p-Akt and poor survival of non-small cell lung cancer patients. In addition, we identified RNF8 as the E3 ligase for regulating the activation of Akt via K63-linked ubiquitination under both physiological and genotoxic conditions, which leads to tumorigenesis and chemoresistance in lung cancer. Our study suggests that RNF8 could be a very promising target in cancer targeted therapy and precision medicine.