PMID- 31528213 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1837-9664 (Print) IS - 1837-9664 (Electronic) IS - 1837-9664 (Linking) VI - 10 IP - 19 DP - 2019 TI - CDK5RAP3 Inhibits the Translocation of MCM6 to Influence the Prognosis in Gastric Cancer. PG - 4488-4498 LID - 10.7150/jca.32208 [doi] AB - 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. FAU - Chen, Qi-Yue AU - Chen QY AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Liu, Li-Chao AU - Liu LC AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Wang, Jia-Bin AU - Wang JB AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Xie, Jian-Wei AU - Xie JW AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Lin, Jian-Xian AU - Lin JX AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Lu, Jun AU - Lu J AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Cao, Long-Long AU - Cao LL AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Lin, Mi AU - Lin M AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Tu, Ru-Hong AU - Tu RH AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Huang, Chang-Ming AU - Huang CM AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Li, Ping AU - Li P AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. FAU - Zheng, Chao-Hui AU - Zheng CH AD - Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China. AD - Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. AD - Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China. LA - eng PT - Journal Article DEP - 20190725 PL - Australia TA - J Cancer JT - Journal of Cancer JID - 101535920 PMC - PMC6746120 OTO - NOTNLM OT - CDK5RAP3 OT - Gastric cancer OT - MCM6 OT - Survival COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2019/09/19 06:00 MHDA- 2019/09/19 06:01 PMCR- 2019/01/01 CRDT- 2019/09/19 06:00 PHST- 2018/12/12 00:00 [received] PHST- 2019/04/29 00:00 [accepted] PHST- 2019/09/19 06:00 [entrez] PHST- 2019/09/19 06:00 [pubmed] PHST- 2019/09/19 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - jcav10p4488 [pii] AID - 10.7150/jca.32208 [doi] PST - epublish SO - J Cancer. 2019 Jul 25;10(19):4488-4498. doi: 10.7150/jca.32208. eCollection 2019.