J Cancer 2019; 10(19):4488-4498. doi:10.7150/jca.32208 This issue

Research Paper

CDK5RAP3 Inhibits the Translocation of MCM6 to Influence the Prognosis in Gastric Cancer

Qi-Yue Chen1,2,3,4#, Li-Chao Liu1,2,3,4#, Jia-Bin Wang1,2,3,4, Jian-Wei Xie1,2,3,4, Jian-Xian Lin1,2,3,4, Jun Lu1,2,3,4, Long-Long Cao1,2,3,4, Mi Lin1,2,3,4, Ru-Hong Tu1,2,3,4, Chang-Ming Huang1,2,3,4✉, Ping Li1,2,3,4✉, Chao-Hui Zheng1,2,3,4✉

1. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
2. Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3. Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
4. Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
# Equal contribution

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Citation:
Chen QY, Liu LC, Wang JB, Xie JW, Lin JX, Lu J, Cao LL, Lin M, Tu RH, Huang CM, Li P, Zheng CH. CDK5RAP3 Inhibits the Translocation of MCM6 to Influence the Prognosis in Gastric Cancer. J Cancer 2019; 10(19):4488-4498. doi:10.7150/jca.32208. Available from https://www.jcancer.org/v10p4488.htm

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Abstract

Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) was identified as a tumor suppressor in gastric cancer, while, minichromosome maintenance complex component 6 (MCM6), which is closely related to the initiation of DNA replication, was reported to be upregulated in multiple malignancies. However, the interaction between these two proteins has not been investigated in gastric cancer. Here, we evaluate the connection between CDK5RAP3 and MCM6 using mass spectrometry and immunoprecipitation. In cells, cell growth and invasiveness indicate that CDK5RAP3 acts as a tumor suppressor by preventing the effects of MCM6. The potential mechanism was revealed using immunofluorescence and nuclear protein extraction. In patients, immunohistochemistry and immunofluorescence show that the protein levels of CDK5RAP3 were markedly decreased in most gastric tumor tissues compared with adjacent nontumor tissues, and the expression levels of MCM6 in the nucleus showed the opposite trend. Prognostic analysis showed that the combined expression of CDK5RAP3 and MCM6 was an independent prognostic factor correlating with the overall survival of gastric cancer patients. Cox regression analysis indicated that the expression of CDK5RAP3 and MCM6 corresponded to T, N, and M stages. Our results demonstrate that CDK5RAP3 can interact with MCM6 and prevent MCM6 from translocating into the nucleus, which may be a potential mechanism through which CDK5RAP3 negatively regulates the proliferation of gastric cancer.

Keywords: CDK5RAP3, MCM6, Gastric cancer, Survival