MCM7 serves as a prognostic marker in diffuse-type gastric adenocarcinoma and siRNA-mediated knockdown suppresses its oncogenic function
MCM7 serves as a prognostic marker in diffuse-type gastric adenocarcinoma and siRNA-mediated knockdown suppresses its oncogenic function
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DOI：
10.3892/or.2014.3094
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发表时间：
2014-05-01
期刊：
影响因子：
4.2
通讯作者：
To, Kafai
中科院分区：
文献类型：
--
作者：
Kang, Wei;Tong, Joanna H. M.;To, Kafai
作为复制前复合体的一部分，MCM7(微型染色体维持蛋白7)对于启动基因组复制是必不可少的。本研究旨在分析其在胃腺癌(GAC)中的表达、临床意义及生物学功能。MCM7蛋白在所有9个GAC细胞系中均表达上调。在6对原发GAC中，MCM7在肿瘤组织中的表达高于相应的非肿瘤胃组织。在正常胃上皮组织中，MCM7严格表达于增殖室。SiRNA下调胃癌细胞株AGS和NCI-N87的MCM7基因后，可显著抑制细胞增殖，抑制单层集落形成，减少细胞侵袭，诱导晚期细胞凋亡。在弥漫型GAC中，其核表达与年龄高、疾病特异性生存差有关。以上结果支持MCM7在胃肿瘤发生中可能起致癌作用。它可作为弥漫型GAC的一个潜在的预后指标和治疗靶点。
MCM7 (mini-chromosome maintenance protein 7) is essential for the initiation of genomic replication as a component of the pre-replication complex. The present study aimed to analyze its expression, clinical significance and biological functions in gastric adenocarcinoma (GAC). The MCM7 protein was upregulated in all 9 GAC cell lines. In 6 paired primary GACs, MCM7 was upregulated in tumor compared with the corresponding non-tumorous gastric tissues. In normal gastric epithelium tissue, MCM7 was strictly expressed in the proliferative compartment. MCM7 knockdown by siRNA in gastric cancer cell line AGS and NCI-N87 significantly suppressed cell proliferation, inhibited monolayer colony formation, reduced cell invasion and induced late apoptosis. Its nuclear expression correlated with advanced age and poorer disease specific survival in diffuse-type GACs. All the findings supported that MCM7 might play an oncogenic role in gastric tumorigenesis. It serves as a potential prognostic marker and therapeutic target in diffuse-type GACs.