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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Helicobacter pylori Infection Modulates the Expression of miRNAs Associated With DNA Mismatch Repair Pathway

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Author(s):
Santos, Juliana C. ; Brianti, Mitsue T. ; Almeida, Victor R. ; Ortega, Manoela M. ; Fischer, Wolfgang ; Haas, Rainer ; Matheu, Ander ; Ribeiro, Marcelo L.
Total Authors: 8
Document type: Journal article
Source: Molecular Carcinogenesis; v. 56, n. 4, p. 1372-1379, APR 2017.
Web of Science Citations: 14
Abstract

Genetic and epigenetic inactivation of DNA mismatch repair (MMR) genes might lead to modifications in cancer-related gene expression and cancer development. Recently, it has been shown that the infection by Helicobacter pylori, the major causative agent of gastric cancer, induces DNA damage and inhibits MMR DNA repair. Also, it has been reported that microRNAs (miRs) have an important role in regulating genomic stability and MMR DNA repair. Thus, the aim of this study was to identify miRs regulating MMR pathway in H. pylori-associated gastric carcinogenesis. To address this question, a gastric epithelial cell line and AGS cancer gastric cells were infected with several H. pylori strains. MMR gene expression and miRs correlating with H. pylori strain infection were evaluated. The results showed that H. pylori infection significantly down-regulated the expression of all selected MMR genes. Also, H. pylori infection modulated the expression of several miRs (including miR-150-5p, miR-155-5p, and miR-3163), after 4, 8, and 12 h of infection. Computational prediction of candidate miRs and their predicted MMR targeting sites were obtained from TargetScan, mirDB, and MetaCore. The generated data indicated that the selected miRs (miR-150-5p, miR-155-5p, and miR-3163) could possibly target and modulate MMR genes (POLD3, MSH2, and MSH3, respectively). The target validation was performed using mimics and luciferase gene reporter assays. Briefly, this study shows that H. pylori impairs MMR DNA repair pathway and identifies miRs that regulate MMR gene expression in gastric cancer. (C) 2016 Wiley Periodicals, Inc. (AU)

FAPESP's process: 14/11862-6 - Evaluation of the regulatory role of genes associated with the via Wnt/b-catenin on the mechanisms of the DNA repair modulated by H. pylori
Grantee:Marcelo Lima Ribeiro
Support Opportunities: Regular Research Grants