Downregulation of miR-7 and miR-153 is involved in Helicobacter pylori CagA induced gastric carcinogenesis and progression

Abstract

Helicobacter pylori (H. pylori) infection plays a pivotal role in the development of gastric cancer (GC). However, the association between aberrant microRNAs (miRNAs/miRs) expression and H. pylori-induced GC remains poorly understood. The present study reported that repeated infection of H. pylori caused the oncogenicity of GES-1 cells in BALB/c Nude mice. miRNA sequencing revealed that both miR-7 and miR-153 were significantly decreased in the cytotoxin-associated gene A (CagA) positive GC tissues and this was further confirmed in a chronic infection model of GES-1/HP cells. Further biological function experiments and in vivo experiments validated that miR-7 and miR-153 can promote apoptosis and autophagy, inhibit proliferation and inflammatory response in GES-1/HP cells. All the associations between miR-7/miR-153 and their potential targets were revealed via bioinformatics prediction and dual-luciferase reporter assay. Particularly, downregulation of both miR-7 and miR-153 obtained an improved sensitivity and specificity in diagnosing H. pylori (CagA+)-induced GC. The present study identified that the combination of miR-7 and miR-153 may be regarded as novel therapeutic targets in H. pylori CagA (+)-associated GC.