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DZNep通过上调miR-200c表达延缓MGC-803胃癌细胞侵袭和迁移过程

宁向红, 郭蓉, 韩磊, 张安玲, 刘茜, 李朝霞, 康春生, 张庆瑜

天津医科大学总医院消化科，天津 300052；天津神经病研究所，神经肿瘤实验室，天津 300052

摘要

本文旨在研究组蛋白甲基化修饰调控对胃癌细胞miR-200c的表达调节以及对癌细胞的侵袭和迁移的作用。组蛋白甲基转移酶抑制剂DZNep (2.5 μmol/L)处理MGC-803胃癌细胞系，用实时定量PCR (qRT-PCR)检测细胞miR-200c的表达变化，用Western blot检测上皮间质转化相关蛋白、EZH2、EED、SUZ12、H3K27me3及MMP9的蛋白表达变化，用细胞划痕实验和Transwell法检测细胞迁移和侵袭。结果显示，与对照(DMSO处理)组相比，DZNep (2.5 μmol/L)处理的MGC-803肿瘤细胞miR-200c基因的表达显著提高，ZEB1、ZEB2、N-cadherin的表达显著下调，E-cadherin的表达上调，EZH2、EED、SUZ12、H3K27me3及MMP9的表达均显著降低，细胞迁移、侵袭能力均减弱。以上结果提示，DZNep通过上调miR-200c的表达延缓胃癌细胞侵袭、迁移过程，其机制涉及对上皮间质转化相关蛋白和PRC2 (polycomb repressive complex 2)的表达调节。

关键词： 胃癌; miR-200c; DZNep; 表观遗传学

分类号：R33

[DZNep raises miR-200c expression to delay the invasion and migration of MGC-803 gastric carcinoma cells.] [Article in Chinese]

NING Xiang-Hong, GUO Rong, HAN Lei, ZHANG An-Ling, LIU Xi, LI Zhao-Xia, KANG Chun-Sheng, ZHANG Qing-Yu

Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China； Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China

Abstract

The aim of the present study was to investigate the regulatory effects of histone methylation modifications on the expression of miR-200c, as well as invasion and migration of gastric carcinoma cells. Gastric carcinoma cell line, MGC-803, were treated by 2.5 μmol/L histone methyltransferase inhibitor, DZNep. The expression of miR-200c was detected by real-time quantitative PCR (qRT-PCR). The epithelial-mesenchymal transition (EMT) indicators (ZEB1/2 and E/N-cadherin), EZH2, EED, SUZ12 and H3K27me3 expressions were detected by Western blot. Cell migration and invasion abilities were detected by Transwell and scratch tests. The result showed that, compared with DMSO (control) group, DZNep significantly increased the expression of miR-200c to about 2.1 times, inhibited ZEB1, ZEB2, and N-cadherin expressions, and activated E-cadherin expression; Also, DZNep decreased the protein expressions of EZH2, EED, SUZ12 and H3K27me3; Moreover, DZNep could inhibit MGC-803 cell invasive and migrative abilities, as well as MMP9 expression. These results suggest DZNep raises miR-200c expression to delay the invasion and migration of gastric carcinoma cells, and the underlying mechanisms involve the regulations of EMT-related proteins and polycomb repressive complex 2.

Key words: gastric carcinoma; miR-200c; DZNep; epigenetics

收稿日期：2014-08-21　　录用日期：2014-11-24

通讯作者：张庆瑜　　E-mail: zhangqy@tijmu.edu.cn

引用本文：

宁向红, 郭蓉, 韩磊, 张安玲, 刘茜, 李朝霞, 康春生, 张庆瑜. DZNep通过上调miR-200c表达延缓MGC-803胃癌细胞侵袭和迁移过程[J]. 生理学报 2015; 67 (1): 83-89.

NING Xiang-Hong, GUO Rong, HAN Lei, ZHANG An-Ling, LIU Xi, LI Zhao-Xia, KANG Chun-Sheng, ZHANG Qing-Yu. [DZNep raises miR-200c expression to delay the invasion and migration of MGC-803 gastric carcinoma cells.] [Article in Chinese]. Acta Physiol Sin 2015; 67 (1): 83-89 (in Chinese with English abstract).