BACKGROUND: Helicobacter pylori is a major human pathogenic bacterium in the gastric mucosa, but to date the regulatory mechanism of the H. pylori-induced inflammatory response is not clear. MicroRNAs have recently emerged as key post-transcriptional regulators of gene expression. We have previously reported that miR-146a negatively regulates the H. pylori-induced inflammatory response, but its molecular mechanism is just beginning to be explored. Our aim was to further explore the key targets of miR-146a and its role of regulation in H. pylori infection. METHODS: The potential targets of miR-146a were screened through bioinformatic approaches and identified by luciferase reporter assays and green fluorescent protein (GFP) repression experiments. Overexpression and inhibition of miR-146a were used to examine the impacts of miR-146a on its target gene, determined by quantitative real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Prostaglandin endoperoxide synthase 2 (PTGS2) is a target gene of miR-146a, and miR-146a decreased PTGS2 expression by degradation of its mRNA, suggesting that the miR-146a-mediated inhibition is a post-transcriptional event. Furthermore, miR-146a and PTGS2 were significantly increased in H. pylori -infected human gastric epithelial cells. Overexpression of miR-146a resulted in significantly reduced PTGS2 production induced by H. pylori infection. CONCLUSIONS: These results suggest that miR-146a may be involved in negatively regulating H. pylori-induced PTGS2 expression in human gastric epithelial cells.
BACKGROUND:Helicobacter pylori is a major human pathogenic bacterium in the gastric mucosa, but to date the regulatory mechanism of the H. pylori-induced inflammatory response is not clear. MicroRNAs have recently emerged as key post-transcriptional regulators of gene expression. We have previously reported that miR-146a negatively regulates the H. pylori-induced inflammatory response, but its molecular mechanism is just beginning to be explored. Our aim was to further explore the key targets of miR-146a and its role of regulation in H. pyloriinfection. METHODS: The potential targets of miR-146a were screened through bioinformatic approaches and identified by luciferase reporter assays and green fluorescent protein (GFP) repression experiments. Overexpression and inhibition of miR-146a were used to examine the impacts of miR-146a on its target gene, determined by quantitative real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Prostaglandin endoperoxide synthase 2 (PTGS2) is a target gene of miR-146a, and miR-146a decreased PTGS2 expression by degradation of its mRNA, suggesting that the miR-146a-mediated inhibition is a post-transcriptional event. Furthermore, miR-146a and PTGS2 were significantly increased in H. pylori -infected human gastric epithelial cells. Overexpression of miR-146a resulted in significantly reduced PTGS2 production induced by H. pyloriinfection. CONCLUSIONS: These results suggest that miR-146a may be involved in negatively regulating H. pylori-induced PTGS2 expression in human gastric epithelial cells.
Authors: Konstantin D Taganov; Mark P Boldin; Kuang-Jung Chang; David Baltimore Journal: Proc Natl Acad Sci U S A Date: 2006-08-02 Impact factor: 11.205
Authors: Jun Lu; Gad Getz; Eric A Miska; Ezequiel Alvarez-Saavedra; Justin Lamb; David Peck; Alejandro Sweet-Cordero; Benjamin L Ebert; Raymond H Mak; Adolfo A Ferrando; James R Downing; Tyler Jacks; H Robert Horvitz; Todd R Golub Journal: Nature Date: 2005-06-09 Impact factor: 49.962
Authors: Simone Backes; Ryan A Langlois; Sonja Schmid; Andrew Varble; Jaehee V Shim; David Sachs; Benjamin R tenOever Journal: Cell Rep Date: 2014-06-19 Impact factor: 9.423