Int J Biol Sci 2020; 16(12):2051-2062. doi:10.7150/ijbs.44119

Research Paper

RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation

Ling Ren1*, Tingting Zhou2*, Yang Wang3, Yanmei Wu3, Hongde Xu2, Jingwei Liu1,2, Xiang Dong2, Fei Yi2, Qiqiang Guo2, Zhuo Wang2, Xiaoman Li2, Ning Bai2, Wendong Guo2, Min Guo2, Bo Jiang2, Xuan Wu2, Yanling Feng2, Xiaoyu Song2, Siyi Zhang2, Yue Zhao4, Liu Cao2✉, Shuai Han5✉, Chengzhong Xing1✉

1. Department of Anorectal Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, RP China
2. Institute of Translational Medicine, College of Basic Medicine, China Medical University, Shenyang 110122, RP China
3. Panjin Liaohe Oilfield Gem FLower Hospital, Panjin 7650036, RP China
4. Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang 110122, RP China
5. Department of Neurosurgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, RP China
*These authors contributed equally to this work.

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Citation:
Ren L, Zhou T, Wang Y, Wu Y, Xu H, Liu J, Dong X, Yi F, Guo Q, Wang Z, Li X, Bai N, Guo W, Guo M, Jiang B, Wu X, Feng Y, Song X, Zhang S, Zhao Y, Cao L, Han S, Xing C. RNF8 induces β-catenin-mediated c-Myc expression and promotes colon cancer proliferation. Int J Biol Sci 2020; 16(12):2051-2062. doi:10.7150/ijbs.44119. Available from http://www.ijbs.com/v16p2051.htm

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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.

Keywords: RNF8, c-Myc, β-catenin, colon cancer