Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Life Sci. 2021 Feb 15;267:118921. doi: 10.1016/j.lfs.2020.118921. Epub 2021 Jan 5.
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.
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.
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/β-catenin signaling pathway, and then promoting tumorigenesis. After silencing TET1, the Wnt/β-catenin signaling pathway which was activated by GGT of Hp was inhibited.
GGT of Helicobacter pylori can promote gastric carcinogenesis by activating Wnt/β-catenin signaling pathway trough up-regulating TET1.
幽门螺杆菌（Hp）感染在胃癌的发展中起着重要作用。Hp 可以分泌γ-谷氨酰转移酶（GGT），然而，Hp 的 GGT 对人类胃细胞的影响尚不清楚。虽然已经证明在胃癌中 ten-eleven 易位 1（TET1）过表达，但 Hp 的 GGT 与 TET1 之间的关系尚未研究。本研究旨在探讨 GGT 与 TET1 之间的关系，并探讨 TET1 在 Hp 诱导胃癌发展中的作用。
通过生物信息学分析 TET1 与胃腺瘤癌预后的相关性。用电穿孔法用质粒敲除 Hp26695 的 GGT 基因，构建 Hp 的 GGT 敲除株（Hp-KS-1）。构建 shTET1 慢病毒转染的 GES-1、MGC-803 和 SGC-7901 细胞系。检测三种细胞的生物学特性。
TET1 在 Hp 感染患者和小鼠的胃组织中过表达。生物信息学分析表明，在胃癌患者中，TET1 表达水平越高，预后越差。Hp 的 GGT 基因可导致 GES-1、MGC-803 和 SGC-7901 细胞中 TET1 的过表达，并激活 Wnt/β-catenin 信号通路，进而促进肿瘤发生。沉默 TET1 后，Hp 的 GGT 激活的 Wnt/β-catenin 信号通路被抑制。
Hp 的 GGT 可通过激活 Wnt/β-catenin 信号通路，上调 TET1，促进胃癌的发生。
