The Gamma-glutamyltransferase gene of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt signal pathway through up-regulating TET1
The Gamma-glutamyltransferase gene of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt signal pathway through up-regulating TET1
复制标题
幽门螺杆菌γ-谷氨酰转移酶基因通过上调TET1激活Wnt信号通路促进胃癌发生
DOI：
10.1016/j.lfs.2020.118921
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发表时间：
2021-01-05
期刊：
影响因子：
6.1
通讯作者：
Lin, Rong
中科院分区：
文献类型：
--
作者：
Meng, Lingjun;Shi, Huiying;Lin, Rong
目的：幽门螺杆菌（Helicobacter pylori，Hp）感染在胃癌的发生发展中起重要作用. Hp能分泌γ-谷氨酰转移酶（GGT），但其GGT对人胃粘膜细胞的影响尚不清楚。虽然已经证实TET 1在胃癌中过表达，但尚未研究Hp的GGT与TET 1之间的关系。本研究旨在探讨GGT与TET 1的关系，以及TET 1在Hp诱导胃癌发生发展中的作用。材料与方法：应用生物信息学方法分析TET 1与胃腺瘤癌预后的相关性。利用质粒电穿孔法敲除Hp 26695的GGT基因，构建Hp GGT敲除菌株（Hp-KS-1）。构建shTET 1慢病毒转染的GES-1、MGC-803和SGC-7901细胞系。主要结果：TET 1在Hp感染患者和小鼠胃组织中均过表达。生物信息学分析表明，TET 1在胃癌患者中的表达越高，预后越差。Hp GGT基因可导致TET 1在GES-1、MGC-803和SGC-7901细胞中过表达，沿着Wnt/beta-catenin信号通路的激活，从而促进肿瘤的发生。意义：幽门螺杆菌GGT通过上调TET 1，激活Wnt/beta-catenin信号通路，促进胃癌的发生。
Aims: Helicobacter pylori (Hp) infection plays an important role in the development of gastric cancer. Hp can secrete gamma-glutamyltransferase (GGT), however, the impact of GGT of Hp on the human gastric cells is not clear. Although it has been demonstrated that ten-eleven translocation 1 (TET1) is overexpressed in gastric cancer, the relationship between the GGT of Hp and TET1 has not been studied. The aim of this study was to explore the relationship between GGT and TET1, and the role of TET1 in the development of gastric cancer induced by Hp was also explored.Materials and methods: The correlation between TET1 and prognosis of gastric adenoma cancer was analyzed by bioinformatics. The GGT gene of Hp26695 was knocked out by electroporation with plasmid to construct the GGT knockout strain of Hp (Hp-KS-1). The shTET1 lentivirus transfected GES-1, MGC-803 and SGC-7901 cell lines were constructed. The biological characteristics of the three kind of cells were detected.Key findings: TET1 was overexpressed in gastric tissues of Hp infected patients and mice. Bioinformatics analysis showed that in patients with gastric cancer, higher TET1 expression would result in poorer prognosis. The GGT gene of Hp can lead to overexpression of TET1 in GES-1, MGC-803 and SGC-7901 cells, along with the activation of Wnt/beta-catenin signaling pathway, and then promoting tumorigenesis. After silencing TET1, the Wnt/beta-catenin signaling pathway which was activated by GGT of Hp was inhibited.Significance: GGT of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt/beta-catenin signaling pathway trough up-regulating TET1.