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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression

Authors: Zhikun Liu, Jie Li, Jun Chen, Qiaonan Shan, Haojiang Dai, Haiyang Xie, Lin Zhou, Xiao Xu, Shusen Zheng

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Minichromosome Maintenance family (MCMs), as replication licensing factors, is involved in the pathogenesis of tumors. Here, we investigated the expression of MCMs and their values in hepatocellular carcinoma (HCC).

Methods

MCMs were analyzed in 105 samples including normal livers (n = 15), cirrhotic livers (n = 40), HCC (n = 50) using quantitative polymerase chain reaction (qPCR) (Cohort 1). Significantly up-regulated MCMs were verified in 102 HCC and matched peritumoral livers using PCR (Cohort 2), and the correlations with clinical features and outcomes were determined. In addition, the focused MCMs were analyzed in parallel immunohistochemistry of 345 samples on spectrum of hepatocarcinogenesis (Cohort 3) and queried for the potential specific role in cell cycle.

Results

MCM2–7, MCM8 and MCM10 was significantly up-regulated in HCC in Cohort 1. In Cohort 2, overexpression of MCM2–7, MCM8 and MCM10 was verified and significantly correlated with each other. Elevated MCM2, MCM6 and MCM7 were associated with adverse tumor features and poorer outcomes. In Cohort 3, MCM6 exhibited superior HCC diagnostic performance compared with MCM2 and MCM7 (AUC: 0.896 vs. 0.675 and 0.771, P < 0.01). Additionally, MCM6 other than MCM2 and MCM7 independently predicted poorer survival in 175 HCC patients. Furthermore, knockdown of MCM6 caused a delay in S/G2-phase progression as evidenced by down-regulation of CDK2, CDK4, CyclinA, CyclinB1, CyclinD1, and CyclinE in HCC cells.

Conclusions

We analyze MCMs mRNA and protein levels in tissue samples during hepatocarcinogenesis. MCM6 is identified as a driver of S/G2 cell cycle progression and a potential diagnostic and prognostic marker in HCC.
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Metadata
Title
MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression
Authors
Zhikun Liu
Jie Li
Jun Chen
Qiaonan Shan
Haojiang Dai
Haiyang Xie
Lin Zhou
Xiao Xu
Shusen Zheng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4056-8

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