PMID- 32403044 OWN - NLM STAT- MEDLINE DCOM- 20210211 LR - 20221207 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 127 DP - 2020 Jul TI - The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population. PG - 110171 LID - S0753-3322(20)30363-2 [pii] LID - 10.1016/j.biopha.2020.110171 [doi] AB - Minichromosome maintenance complex component 6 (MCM6) is involved in tumorigenesis of hepatocellular carcinoma (HCC). Because its effect on different populations remains unclear, this study investigated the impact of MCM6 on HCC in Southern Chinese Zhuang population. In addition to assessing the global mRNA levels of MCM6 based on The Cancer Genome Atlas database (TCGA) and The Gene Expression Omnibus database (GEO), associations between MCM6 mRNA levels and clinicopathological features were analyzed. High MCM6 levels were associated with high alpha-fetoprotein (AFP) (>20 ng/mL in serum) (P < 0.0001) and advanced clinical stage (III + IV) (P < 0.001). Higher MCM6 was associated with poorer outcomes (P < 0.01) in these databases. Furthermore, the mRNA and protein expression of MCM6 in the Guangxi Zhuang population was detected by quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC). The results showed that MCM6 levels were up-regulated in the Zhuang population with HCC. Higher MCM6 protein levels were correlated with larger tumor size (>5 cm) (P = 0.038) and advanced clinical stage (III + IV) (p = 0.023). Bioinformatic enrichment analysis of MCM6 and its interacting proteins (CDT1,WEE1,TRIM28 and MKI67) suggested that in addition to being involved in the cell cycle process, these complexes could also be involved in protein binding, pre-replication complex assemble, and nucleus metabolism. Based on the protein-protein interaction (PPI) network with module screen, the interactions between MCM6 and its potential interacting proteins were further studied through protein docking with hot spot analysis. Additionally, the results of the algorithms combining the ROC of MCM6 and its interacting proteins showed that combination biomarker analysis has better HCC diagnosis ability than the single MCM6 test. The combination of MCM6 and TRIM28 was more suitable for the Guangxi Zhuang population. Overall, our study suggests that MCM6 plays an important role in the growth of HCC. MCM6 could be an optimal biomarker for diagnosing HCC and a potential molecular target for HCC therapy in the Zhuang population. CI - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Jia, Wenxian AU - Jia W AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China; Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China. FAU - Xie, Li AU - Xie L AD - Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. FAU - Wang, Xiao AU - Wang X AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China; Department of Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. FAU - Zhang, Qinle AU - Zhang Q AD - Genetic and Metabolic Central Laboratory, The Maternal and Children Health Hospital of Guangxi, Guangxi, China. FAU - Wei, Bing AU - Wei B AD - College of International Education, Guilin Medical University, Guilin, Guangxi, China. FAU - Li, Hongwen AU - Li H AD - Teaching and Researching Section of Human Anatomy, Guilin Medical University, Guilin, Guangxi, China. FAU - Qin, Shouxu AU - Qin S AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. FAU - Chen, Suixia AU - Chen S AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. FAU - Liu, Jiayi AU - Liu J AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. FAU - Tan, Yanjun AU - Tan Y AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. FAU - Zheng, Shengfeng AU - Zheng S AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. FAU - Liang, Xiaonan AU - Liang X AD - Department of Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: lxn120@126.com. FAU - Yang, Xiaoli AU - Yang X AD - Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China. Electronic address: cncsyxl@126.com. LA - eng PT - Journal Article DEP - 20200508 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (AFP protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (RNA, Messenger) RN - 0 (alpha-Fetoproteins) RN - EC 2.3.2.27 (TRIM28 protein, human) RN - EC 2.3.2.27 (Tripartite Motif-Containing Protein 28) RN - EC 3.6.4.12 (MCM6 protein, human) RN - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6) SB - IM MH - Adult MH - Asian People MH - Biomarkers, Tumor/metabolism MH - Carcinoma, Hepatocellular/genetics/*pathology MH - China MH - Computational Biology MH - Female MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Liver Neoplasms/genetics/*pathology MH - Male MH - Middle Aged MH - Minichromosome Maintenance Complex Component 6/*genetics MH - Neoplasm Staging MH - Protein Interaction Maps MH - RNA, Messenger/genetics MH - Tripartite Motif-Containing Protein 28/genetics MH - alpha-Fetoproteins/metabolism OTO - NOTNLM OT - Bioinformatics enrichment OT - Diagnosis OT - Hepatocellular carcinoma OT - MCM6 OT - Molecular docking OT - Zhuang population COIS- Declaration of Competing Interest The authors declare that there is no conflict of interest. EDAT- 2020/05/14 06:00 MHDA- 2021/02/12 06:00 CRDT- 2020/05/14 06:00 PHST- 2019/09/17 00:00 [received] PHST- 2020/04/04 00:00 [revised] PHST- 2020/04/13 00:00 [accepted] PHST- 2020/05/14 06:00 [pubmed] PHST- 2021/02/12 06:00 [medline] PHST- 2020/05/14 06:00 [entrez] AID - S0753-3322(20)30363-2 [pii] AID - 10.1016/j.biopha.2020.110171 [doi] PST - ppublish SO - Biomed Pharmacother. 2020 Jul;127:110171. doi: 10.1016/j.biopha.2020.110171. Epub 2020 May 8.