Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, People's Republic of China; Department of Anatomy, School of Medicine, University of South China, Hengyang, Hunan Province, People's Republic of China.
Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, People's Republic of China.
Exp Cell Res. 2018 Jun 15;367(2):196-204. doi: 10.1016/j.yexcr.2018.03.036. Epub 2018 Mar 29.
It has been found that Helicobacter pylori （H. pylori）is not only the main cause of gastric cancer, but also closely related to its metastasis. E-cadherin cleavage induced by matrix metalloproteinases (MMPs) plays an important role in the tumor metastasis. In the present study, we investigated the role of microRNAs-MMPs-E-cadherin in migration and invasion of gastric cancer cells treated with H. pylori. The results showed that H. pylori induced migration and invasion of SGC-7901 cells with a down-regulation of E-cadherin expression, which were abolished by MMPs knock down, E-cadherin overexpression, mimics of miR128 and miR148a. MiR128/miR148a inhibitors restored MMP-3/MMP-7 expression, down-regulated E-cadherin level, and accelerated cellular migration and invasion. This study suggests that H. pylori induces migration and invasion of gastric cancer cells through reduction of E-cadherin function by activation of MMP-3, - 7. The present results also suggest that the activated MMPs/E-cadherin pathway is related with down-regulation of miR128/miR148a in the human gastric cancer cells infected with H. pylori.
已经发现，幽门螺杆菌（H. pylori）不仅是胃癌的主要病因，还与胃癌的转移密切相关。基质金属蛋白酶（MMPs）诱导的 E-钙黏蛋白裂解在肿瘤转移中起重要作用。本研究探讨了 microRNAs-MMPs-E-钙黏蛋白在 H. pylori 处理的胃癌细胞迁移和侵袭中的作用。结果表明，H. pylori 诱导 SGC-7901 细胞迁移和侵袭，同时下调 E-钙黏蛋白表达，而 MMPs 敲低、E-钙黏蛋白过表达、miR128 和 miR148a 的模拟物可消除这种作用。miR128/miR148a 抑制剂恢复 MMP-3/MMP-7 表达，下调 E-钙黏蛋白水平，并加速细胞迁移和侵袭。本研究表明，H. pylori 通过激活 MMP-3、-7 降低 E-钙黏蛋白功能，诱导胃癌细胞迁移和侵袭。本研究还表明，在感染 H. pylori 的人胃癌细胞中，激活的 MMPs/E-钙黏蛋白通路与 miR128/miR148a 的下调有关。
