Helicobacter pylori infection impairs gastric epithelial barrier function via microRNA-100-mediated mTOR signaling inhibition

Abstract

Helicobacter pylori (H. pylori) infection has an important effect on human health as it is an established cause of gastric carcinoma. microRNAs (miRNAs/miRs) are a family of small RNAs with various functions in the control of cellular profiles. However, the effect of miR-100 in H. pylori infection remains unknown. Healthy volunteers (n=100) and patients with H. pylori infection (n=98) were included in the present study. H. pylori infection was confirmed by urea breath tests. The levels of miR-100 in gastroscopic biopsy samples and cultured GES-1 cells were measured by reverse transcription-quantitative polymerase chain reaction. Furthermore, miR-100 was overexpressed or inhibited in GES-1 cells by an miR-100 mimic or inhibitor, respectively. The expression of cell-junction proteins and members of the mechanistic target of rapamycin kinase (mTOR) signaling pathway was investigated by western blotting. The results demonstrated that miR-100 levels were upregulated in infected patients and cultured gastric epithelial cells, compared with the respective controls. Additionally, the expression of epithelial (E)-cadherin and zona occludens-1 in the gastric mucosa of infected patients and GES-1 cells was downregulated. Furthermore, infected gastric epithelial cells exhibited impaired barrier functions, as measured by resistance and permeability tests. Overexpression of miR-100 inhibited junction protein expression, as well as the activation of the mTOR signaling pathway, while suppression of miR-100 restored E-cadherin expression and mTOR signaling. The results of the present study indicate that H. pylori infection may cause dysfunction of the gastric epithelial barrier by increasing miR-100 levels, which subsequently inhibit mTOR signaling. These results may have potential applications affecting miR-100 in H. pylori-related diseases.