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MCM7作为弥漫型胃腺癌的预后标志物,且小干扰RNA介导的敲低可抑制其致癌功能。

MCM7 serves as a prognostic marker in diffuse-type gastric adenocarcinoma and siRNA-mediated knockdown suppresses its oncogenic function.

作者信息

Kang Wei, Tong Joanna H M, Chan Anthony W H, Cheng Alfred S L, Yu Jun, To Kafai

机构信息

Department of Anatomical and Cellular Pathology, State Key Laboratory in Oncology in South China, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.

School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, P.R. China.

出版信息

Oncol Rep. 2014 May;31(5):2071-8. doi: 10.3892/or.2014.3094. Epub 2014 Mar 19.

Abstract

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.

摘要

MCM7(微小染色体维持蛋白7)作为复制前复合体的一个组成部分,对基因组复制的起始至关重要。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。在所有9种GAC细胞系中,MCM7蛋白均上调。在6对原发性GAC中,与相应的非肿瘤性胃组织相比,肿瘤中MCM7上调。在正常胃上皮组织中,MCM7严格表达于增殖区室。通过小干扰RNA(siRNA)敲低胃癌细胞系AGS和NCI-N87中的MCM7,可显著抑制细胞增殖、抑制单层集落形成、减少细胞侵袭并诱导晚期凋亡。在弥漫型GAC中,其核表达与高龄及较差的疾病特异性生存相关。所有这些发现均支持MCM7可能在胃肿瘤发生中发挥致癌作用。它可作为弥漫型GAC潜在的预后标志物和治疗靶点。

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