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.

ceRNA network construction and comparison of gastric cancer with or without Helicobacter pylori infection

“…Downregulation of miR128/miR148a in H. pylori (+) GC results in the activation of the MMPs/E-cadherin pathway and induces migration and invasion of GC cells (Yang, Li, Du, Yin, & Li, 2018). H. pylori infection may also cause dysfunction of the gastric epithelial barrier by increasing miR-100 levels (Hu, Guo, & Ye, 2018). miR-195 and miR-488 appear to play pivotal roles in controlling IL-6 activity in H. pylori infection (Chung et al, 2017).…”

Overexpression of Rictor protein and Rictor-H. pylori interaction has impact on tumor progression and prognosis in patients with gastric cancer

“…There is evidence that H. pylori infection is identified as a beneficial prognostic indicator for GC, indicating different growth patterns between H. pylori (+) and H. pylori (-) GC [12][13]. Meanwhile, the infection of H. pylori is associated with mTOR signaling [14][15]. Relatively little is known about whether there is an interaction between Rictor expression and H. pylori status in the prognosis of GC.…”

Rabeprazole destroyed gastric epithelial barrier function through FOXF1/STAT3‐mediated ZO‐1 expression

“…Consistent with this, H. pylori induced elevation of PTEN promoter methylation, thus attenuating the PTEN expression, which further led to increased proliferation and inhibited apoptosis of HGC-27 cells,36 furthermore, H. pylori induced gastric cell proliferation associated with its CagA translocation in BGC823 and SGC7901 cells via attenuation of NF-κB-mediated CEACAM1 variant 3S (CEACAM1-3S) expression, which is inhibited by MUC17, a main components of gastric mucosal barrier consisted of a family of high molecular-weight glycoproteins expressed by specialized epithelial cells as secreted or membranebound mucins 37. H. pylori infection resulted in upregulation of miR-100 expression in GES-1 cells, which subsequently decreased zona occludens-1(ZO-1) and E-cadherin expression through mTOR signalling 38. Interestingly, our present study demonstrates that Rabeprazolestimulation decreased ZO-1, E-cadherin and Occludin 1 expression, leading to the destruction of barrier function as evidenced by decreased resistance observed in monolayer gastric epithelial cells coculture with Rabeprazole.…”