肿瘤抑制基因5在人低分化胃腺癌发生过程中的调控机制及其分子水平差异的研究

华应刚; 李茵; 易梦婷; 李剑; 蔡良良; 蒙明慧; 曾骥孟; 刘国彦

doi:10.3760/cma.j.issn.1001-9030.2016.06.062

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中华实验外科杂志

• 临床研究 •

ENGLISH ABSTRACT

肿瘤抑制基因5在人低分化胃腺癌发生过程中的调控机制及其分子水平差异的研究

作者及单位信息

出版日期： 2016 -06 -08 ·

DOI： 10.3760/cma.j.issn.1001-9030.2016.06.062

The tumor suppressor gene 5 in the study of differences in regulatory mechanisms and the molecular level in the process of human gastric cancer

Authors Info & Affiliations

Hua Yinggang

Department of Gastrointestinal Surgery, Zhong Shan Hospital, Xiamen University, Xiamen 361004, China

Li Yin

International Traveller Healththy Center of Xiamen, Xiamen 361012, China

Yi Mengting

Department of Gastrointestinal Surgery, Zhong Shan Hospital, Xiamen University, Xiamen 361004, China

Li Jian

School of Pharmaceutical Sciences Xiamen University, Xiamen 361005, China

Cai Liangliang

School of Pharmaceutical Sciences Xiamen University, Xiamen 361005, China

Meng Minghui

Innova Biological Medicine Company, Yangzhou 550004, China

Zeng Jimeng

School of Pharmaceutical Sciences Xiamen University, Xiamen 361005, China

Liu Guoyan

Department of Gastrointestinal Surgery, Zhong Shan Hospital, Xiamen University, Xiamen 361004, China

Published： 2016 -06 -08 ·

DOI： 10.3760/cma.j.issn.1001-9030.2016.06.062

289

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摘要

目的探讨肿瘤抑制基因5(ST5)在低分化胃腺癌发生中的作用。

方法应用甲基化芯片技术来建立人低分化胃腺癌甲基化谱，分析ST5基因在人低分化胃癌组织中甲基化。用分子生物学方法对人低分化胃腺癌样本和正常胃组织样本，以及胃相关细胞株中ST5基因表达进行分析。

结果在表观遗传学水平，ST5基因在人低分化胃腺癌组织中显著高甲基化；在mRNA水平，ST5基因在低分化胃腺癌细胞株SGC-7901中表达量低 (倍数变化为0.61， P<0.01)；在蛋白质水平，ST5基因在人低分化胃腺癌组织中表达较低，且在人低分化胃腺癌细胞株BGC-823、MGC-803和SGC-7901细胞株中表达量亦较低。

结论ST5基因在人低分化胃腺癌中发挥其抑癌基因的作用，而该作用由于高甲基化被抑制。

关键词：人低分化胃腺癌;基因甲基化芯片;肿瘤抑制基因5

ABSTRACT

ObjectiveTo explore the role of tumor suppresser gene tumor suppressor gene 5 (ST5) in the occurrence of gastric adenocarcinoma.

MethodsDNA methylation chip and bioinformatic analysis were applied to deep the different genes between diffused gastric adenocarcinoma and normal gastric tissues. The mRNA and protein expression level of ST5 gene were detected by reverse transcription-polymerase chain reaction (RT-PCR) and westen-blot in gastric adenocarcinoma tissues and gastric cancer cell lines.

ResultsThe ST5 gene showed significant high methylation in diffused gastric adenocarcinoma; the mRNA expression level of ST5 gene was lower in poorly differentiated SGC-7901 stomach cancer cell lines (fold change=0.61, P<0.01); ST5 gene was demonstrated lower protein expression level in diffused gastric adenocarcinoma tissue and cell lines like BGC-823, MGC-803 and SGC-7901.

ConclusionThe ST5 gene represented as a tumor suppressor gene, playing an important role in gastric cancerization via regulation of DNA methylation.

KEYWORDS： Human gastric cancer;DNA methylation chip;Tumor suppressor gene 5

Corresponding author: Zeng Jimeng, Email: nc.defudabe.umxgneztmc

Corresponding author:Liu Guoyan, Email: mocdef.3ab612950rd

FUNDING:

National Natural Science Foundation of China (81272445)

COPYRIGHTS:

No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.

All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

华应刚,李茵,易梦婷,等. 肿瘤抑制基因5在人低分化胃腺癌发生过程中的调控机制及其分子水平差异的研究[J]. 中华实验外科杂志,2016,33(6)：1638-1640.

DOI:10.3760/cma.j.issn.1001-9030.2016.06.062

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胃癌是在世界范围内的高发肿瘤，其死亡率在所有肿瘤中占第4位 ^{[
1
]}。根据肿瘤起源分型将胃癌分为"肠型"和"弥漫型" ^{[
2
,

3
]}，其中亚洲国家以弥漫型胃癌 ^{[
4
,

5
]}多见，而西方国家则以肠型胃癌多见 ^{[
6
,

7
,

8
]}。两型胃腺癌发病的不同阶段，流行病学致病因素和由此产生的基因、分子改变有很大差异，但目前对于"弥散型"胃癌所知甚少，其发生和进展机制还有待研究。胃癌的发生、发展与癌基因的激活和肿瘤抑制基因的失活有直接关系 ^{[
9
]}，目前普遍认为DNA甲基化是除了缺失和突变之外导致肿瘤抑制基因失活的另一种机制。研究结果报道，肿瘤抑制基因5(ST5)是一种肿瘤抑制基因，ST5基因在肿瘤的发生中发挥重要作用 ^{[
10
,

11
,

12
]}。本研究旨在探讨肿瘤抑制基因的甲基化及其对该基因的调控对胃癌的意义。

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备注信息

通信作者：曾骥孟，Email： nc.defudabe.umxgneztmc

通信作者：刘国彦，Email： mocdef.3ab612950rd

基金项目：

国家自然科学基金 (81272445) 查看更多基金信息

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