Qu Kai, Wang Zhixin, Fan Haining, Li Juan, Liu Jie, Li Pingping, Liang Zheyong, An Hongli, Jiang Yina, Lin Qiushi, Dong Xiaoqun, Liu Peijun, Liu Chang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining 810001, Qinghai Province, China.
Cell Death Dis. 2017 Feb 9;8(2):e2603. doi: 10.1038/cddis.2016.352.
DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients. Mechanistically, knockdown of MCM7 significantly inhibited cellular proliferation in vitro and HCC tumorigenicity in vivo. Cyclin D1 was proved to be regulated by MCM7-MAPK signaling pathway. Clinically, high expression of both MCM7 and cyclin D1 exhibited a relatively high sensitivity and specificity to predict worse outcome of HCC patients. Taken together, our results suggest that MCM7-cyclin D1 pathway may participate in cancer progression and serve as a biomarker for prognosis in HCC.
DNA复制是细胞增殖的核心过程,而异常的DNA复制被认为是肿瘤发生的驱动力。微小染色体维持复合物组分7(MCM7)在启动DNA复制中起重要作用。为了研究MCM7在肝细胞癌(HCC)中的潜在致癌特性和预后价值,我们对153例HCC样本进行了MCM7免疫组织化学染色,发现MCM7高表达水平与HCC患者较差的总生存期(OS)相关。机制上,敲低MCM7可显著抑制体外细胞增殖和体内HCC致瘤性。细胞周期蛋白D1被证明受MCM7-MAPK信号通路调控。临床上,MCM7和细胞周期蛋白D1的高表达在预测HCC患者较差预后方面表现出相对较高的敏感性和特异性。综上所述,我们的结果表明MCM7-细胞周期蛋白D1通路可能参与癌症进展,并可作为HCC预后的生物标志物。