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MCM7 promotes cancer progression through cyclin D1-dependent signaling and serves as a prognostic marker for patients with hepatocellular carcinoma

机译:MCM7通过细胞周期蛋白D1依赖性信号传导促进癌症进展并作为肝细胞癌患者的预后标志物

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摘要

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.
机译:DNA复制是细胞增殖的主要过程,而异常的DNA复制被认为是致癌作用的驱动力。微型染色体维持复合物组件7(MCM7)在启动DNA复制中起着至关重要的作用。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患者较差的总生存率(OS)相关。从机制上讲,敲低MCM7可以显着抑制体外细胞增殖和体内HCC致瘤性。 Cyclin D1被证实受MCM7–MAPK信号通路的调节。临床上,MCM7和细胞周期蛋白D1的高表达表现出较高的敏感性和特异性,可预测HCC患者的预后不良。综上所述,我们的结果表明,MCM7–cyclin D1途径可能参与癌症进展,并成为预后的肝癌生物标志物。

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