Induction of microRNA‐155 duringHelicobacter pyloriInfection and Its Negative Regulatory Role in the Inflammatory Response

Abstract

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression at posttranscriptional level. H. pylori is a major human pathogenic bacterium in gastric mucosa. To date, the role of miRNAs in response to H. pylori infection has not been explored. The expression profile of cellular miRNAs during H. pylori infection was analyzed by using microarray and quantitative reverse-transcriptase polymerase chain reaction. The potential target of miR-155 was identified by luciferase assay and Western blot. Promoter analysis and inhibitor experiment were used to investigate the pathway involved in the induction of miR-155. Examination of miR-155 function was performed by overexpression and inhibition of miR-155. H. pylori was able to increase the miR-155 expression in gastric epithelial cell lines and gastric mucosal tissues, and nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) pathway were required for the induction of miR-155. miR-155 may down-regulate IkappaB kinase epsilon, Sma- and Mad-related protein 2 (SMAD2), and Fas-associated death domain protein. Furthermore, the overexpression of miR-155 negatively regulated the release of interleukin-8 and growth-related oncogene-alpha. This study provides the first description of increased expression of miR-155 in H. pylori infection, and miR-155 may function as novel negative regulator that help to fine-tune the inflammation response of H. pylori infection.