RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation
Ling Ren, Tingting Zhou, Yang Wang, Yanmei Wu, Hongde Xu, Jingwei Liu, Xiang Da Dong, Fei Yi, Qiqiang Guo, Zhuo Wang, Xiaoman Li, Ning Bai, Wendong Guo, Min Guo, Bo Jiang, Xuan Wu, Yanling Feng, Xiaoyu Song, Siyi Zhang, Yue Zhao, Liu Cao, Shuai Han, Chengzhong Xing
Abstract
DNA damage signals transducer RING finger protein 8 (RNF8) is involved in maintaining genomic stability by facilitating the repair of DNA double-strand breaks (DSB) via ubiquitin signaling. By analyzing the TCGA database and colon cancer tissue microarrays, we found that the expression level of RNF8 was positively correlated with that of c-Myc in colon cancer, which were closely associated with poor survival of colon cancer patients. Furthermore, overexpressing and knocking down RNF8 increased and decreased the expression of c-Myc in colon cancer cells, respectively. In addition, RNF8 interacted with β-catenin and facilitated its nuclear translocation by conjugating K63 polyubiquitination on it. These observations suggested a de novo role of RNF8 in promoting the progression of colon cancer by inducing β-catenin-mediated c-Myc expression.