Helicobacter pylori induced miR-362-5p upregulation drives gastric cancer progression and links hepatocellular carcinoma through an exosome-dependent pathway.

INTRODUCTION: Helicobacter pylori (H. pylori) infection induced miRNA dysregulation plays an important role in gastric cancer (GC) and exosomes mediate the spread of pathogenic effects. METHODS: Expression of miR-362-5p and its clinical significance in GC were analyzed using data from TCGA. The effects of miR-362-5p on GC cells' proliferation and migration were examined by using CCK-8, EdU, transwell and scratch assays. MKN45 xenograft model in nude mice was employed to evaluate impacts of miR-362-5p on GC progression in vivo. Target gene of miR-362-5p was screened by bioinformatic analysis and verified by using dual-luciferase assay. Exosomes from H. pylori-infected GES-1 cell (Hp-GES-EVs) were isolated and miR-362-5p inside the exosome was detected. The uptake of exosome by GC cells was observed through fluorescence imaging and exosome-mediated pathogenesis was explored. Furthermore, the transport of exosome-mediated miR-362-5p via blood was examined. The effect of exosome-carried miR-362-5p on hepatocellular carcinoma (HCC) progression was investigated by hepatocyte's uptake, proliferation and migration assays. RESULTS: miR-362-5p was significantly upregulated in GC tissues associated with H. pylori infection. Downregulation of miR-362-5p in GC cells inhibited proliferation and migration in vitro and suppressed tumor growth in vivo, counteracting H. pylori-induced carcinogenesis. TLE4 was confirmed as a direct target of miR-362-5p, and miR-362-5p/TLE4 axis implicated in H. pylori-driven neoplastic transformations in GC cells. Hp-GES-EVs mediated the transport of miR-362-5p, was absorbed by GC cells and detected at elevated levels in the serum of infected mice. Moreover, Hp-GES-EVs were diffused to liver and taken up by liver cells, enhancing HCC cell proliferation and migration by targeting TLE4. CONCLUSION: H. pylori infection upregulates miR-362-5p, facilitating GC progression via TLE4 targeting. Exosome-mediated transfer amplifies its effects, contributing to liver damage and potentially facilitating HCC.