Helicobacter pylori outer membrane vesicle-induced hsa-miR-302a-3p and hsa-miR-184 promote the occurrence and development of gastric cancer.

Helicobacter pylori (H. pylori) is a major gastric cancer pathogen. Recent studies have linked H. pylori infection to microRNA (miRNA) dysregulation. H. pylori outer membrane vesicles (OMVs) support bacterial survival and pathogenesis, but the OMV-miRNA interactions remain unclear. To address this lack of understanding, we co-cultured the H. pylori strain NCTC11637 and its OMVs with the gastric epithelial cell line GES-1 and gastric cancer cell lines SGC-7901 and HGC-27. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) showed hsa-miR-302a-3p upregulation in the GES-1 line and hsa-miR-184 upregulation in the SGC-7901 and HGC-27 lines. To explore the OMV-miRNA mechanisms, we built transfected models: GES-1 with hsa-miR-302a-3p overexpression and SGC-7901 and HGC-27 with hsa-miR-184 overexpression or inhibition. The experimental study on the malignant behavior of tumors (i.e., proliferation, migration, invasion, and clonogenic assay) showed enhanced malignant phenotypes in the overexpressed cells. Hsa-miR-184 inhibition reversed these effects in the cancer cells. Intriguingly, hsa-miR-302a-3p overexpression in the GES-1 cells enhanced tumorigenesis via anchorage-independent growth, which is a key carcinogenic trait. Next, we identified differential proteins in the overexpressed cells via proteomic mass spectrometry. Finally, we validated the target proteins and analyzed the signaling pathways to elucidate the mechanisms. We found that H. pylori OMV-induced hsa-miR-302a-3p upregulation may promote gastric cancer initiation, while hsa-miR-184 overexpression may drive progression. This study provides a basis for the diagnosis and treatment of gastric cancer.