Helicobacter pylori infection upregulates miR-135b-5p to stimulate gastric cancer cell proliferation and inhibit cell apoptosis through activated IL-6/STAT3 signaling

Abstract Background Helicobacter pylori (H. pylori) infection is a strong pathogenic factor of gastric cancer (GC). The dysregulation of microRNAs (miRNAs) has been correlated with gastric tumorigenesis, but their role in H. pylori-induced GC remains inadequately evaluated. Methods In situ hybridization was performed for evaluation of miR-135b-5p expression in GC patients. MTS assay, EdU cell imaging assay, live cell imaging and flow cytometric analysis were achieved for functional assessment of miR-135b-5p. Quantitative real-time PCR, western blot, chromatin immunoprecipitation, luciferase reporter assay and immunohistochemistry were used for exploration of regulatory mechanism and identification of target gene. Results Our study indicated that miR-135b-5p expression was increased in GC patients, and overexpression of miR-135b-5p stimulated GC cells proliferation and inhibits cell apoptosis. Mechanistically, H. pylori infection increased miR-135b-5p expression through the activation of the IL-6/STAT3 signaling, and STAT3 regulates miR-135b-5p via binding to its promoter directly. Furthermore, miR-135b-5p promoted GC progression by interfering TXNIP 3’ untranslated region and suppressing its protein expression, thereby affecting AKT phosphorylation. Expression of TXNIP was decreased in GC patients, and low expression levels of TXNIP in human GC patients is correlated with poor survival. Conclusions Our findings revealed a mechanism that H. pylori infection stimulates upregulation of miR-135b-5p via IL-6/STAT3 signaling and promotes gastric carcinogenesis, which brings up a promising diagnostic biomarker and provides an insight into therapeutic strategies for H. pylori-associated GC.