miR-155 and miR-146b negatively regulates IL6 in Helicobacter pylori (cagA+) infected gastroduodenal ulcer.

OBJECTIVE

Helicobacter pylori (H. pylori) infection is the main cause of gastroduodenal ulcer. The molecular mechanisms that underlying this progress are still not very clear. MicroRNAs (miRNAs) are small noncoding RNAs that function as negative regulator of numerous target genes at posttranscriptional level. miRNAs plays important roles in the development of many infection related diseases. The roles of miRNAs in the development of H. pylori-infected gastroduodenal ulcer haven't been well studied yet.

MATERIALS AND METHODS

The miRNA and mRNA profiles in normal gastroduodenal biopsy, H. pylori-infected gastroduodenal biopsy and H. pylori-infected gastroduodenal ulcer biopsy samples were compared and analyzed to identify potential related miRNAs and their target genes. The differential expression of the identified miRNAs and their target gene were validated in an independent set of H. pylori positive gastroduodenal ulcer biopsy samples by immunohistochemistry staining and RT-PCR. Then microRNA mimics were transfected to gastric epithelial cells infected with H. pylori 26695 (cagA+). RT-PCR and Western blotting were performed to confirm the target gene of the identified microRNAs.

RESULTS

The integrative analysis and immunohistochemistry staining validation indicated that miR-155 and miR-146b, as well as their predicted target gene IL6, are up-regulated in H. pylori positive gastroduodenal ulcer. Further experiments in gastric epithelial cells revealed that H. pylori 26695 (cagA+) infection induces IL6 overexpression. But the overexpression of IL6 is weaken due to negative regulation by miR-155 and miR-146b.

CONCLUSIONS

This study indicated that the up-regulation of miR-155 and miR-146b decreases H. pylori (cagA+)-introduced IL6 overexpression, which might weaken the cleanup of H. pylori (cagA+) and contributes to ulcer.