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The impact of MCM6 on hepatocellular carcinoma in a Southern Chinese Zhuang population - 30/05/20

Doi : 10.1016/j.biopha.2020.110171 
Wenxian Jia a, b, 1, Li Xie c, 1, Xiao Wang a, d, 1, Qinle Zhang e, 1, Bing Wei f, Hongwen Li g, Shouxu Qin a, Suixia Chen a, Jiayi Liu a, Yanjun Tan a, Shengfeng Zheng a, Xiaonan Liang d, , Xiaoli Yang a,
a Scientific Research Center, Guilin Medical University, Guilin, Guangxi, China 
b Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi, China 
c Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 
d Department of Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 
e Genetic and Metabolic Central Laboratory, The Maternal and Children Health Hospital of Guangxi, Guangxi, China 
f College of International Education, Guilin Medical University, Guilin, Guangxi, China 
g Teaching and Researching Section of Human Anatomy, Guilin Medical University, Guilin, Guangxi, China 

Corresponding authors.

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Highlights

High MCM6 with significant clinical features is found in Southern Chinese Zhuang populations with hepatocellular carcinoma.
MCM6 and its interacting proteins could involve in protein binding, pre-replication complex assemble, and nucleus metabolism.
Abundant binding sites on MCM6 and its target proteins are detected.
Diagnostic values of MCM6 and its interacting proteins are assessed in TCGA and Southern Chinese Zhuang populations.
Combination of MCM6 and TRIM28 is more suitable for hepatocellular carcinoma diagnosis in Southern Chinese Zhuang populations.

Le texte complet de cet article est disponible en PDF.

Abstract

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.

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Keywords : MCM6, Hepatocellular carcinoma, Zhuang population, Diagnosis, Bioinformatics enrichment, Molecular docking


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Vol 127

Article 110171- juillet 2020 Retour au numéro
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