Helicobacter pylori-induced miR-136 is a potential predictor of early-stage gastric cancer

MicroRNAs play an important role in gastric cancer (GC) development following Helicobacter pylori (H. pylori) infection. Yet the exact mechanism is still not fully understood. Herein, we investigated the underlying mechanisms of miR-136 during this process.

To investigate the role of miR-136 in H. pylori-induced GC progression.

GC and gastric epithelial cells were infected with H. pylori and transfected with miR-136 mimic, inhibitor, mimic plus PDCD11 (identified as miR-136 target), or miR-NC (control). Cell proliferation, migration, and invasion were assessed via cell counting kit-8 assay, colony formation, wound healing, and Transwell assays. Nuclear factor kappa-B (NF-κB)/miR-136/PDCD11 interactions were confirmed by luciferase and inhibition assays. For in vivo studies H. pylori-infected BGC-823 cells were injected into nude mice. Reverse transcription PCR, western blot, immunohistochemistry, and immunofluorescent staining assay were used to assess mRNA and protein expression.

miR-136 expression was significantly upregulated while PDCD11 expression was significantly downregulated in early GC tissues and GC cells infected with H. pylori compared with non-infected tissues or cells (all P < 0.01). miR-136 overexpression induced by H. pylori could promote the proliferation and migration of infected GC cells and induce the growth of H. pylori-positive GC tumors in mice while its inhibition could reverse this effect. Mechanistically, upregulation of miR-136 suppressed PDCD11 through NF-κB activation induced by H. pylori infection.

miR-136 is a novel diagnostic biomarker and therapeutic target in H. pylori-associated early-stage gastric carcinogenesis and acts through the NF-κB-miR-136-PDCD11 pathway.