Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway

Molecular Carcinogenesis - Tập 56 Số 4 - Trang 1372-1379 - 2017
Juliana C. Santos1,2, Mitsue Taukeuti Brianti1, Victor R. de Almeida1, Manoela Marques Ortega1, Wolfgang Fischer3, Rainer Haas3, Ander Matheu4, Marcelo Lima Ribeiro1
1Clinical Pharmacology and Gastroenterology Unit São Francisco University Medical School São Francisco University Bragança Paulista São Paulo Brazil
2Women's Integrated Healthcare Center (CAISM) State University of Campinas (UNICAMP) Campinas São Paulo Brazil
3Max von Pettenkofer‐Institut Ludwig‐Maximilians‐Universität München Germany
4Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, and IKERBASQUE, Basque Foundation, Bilbao, Spain

Tóm tắt

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. © 2016 Wiley Periodicals, Inc.

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Molecular Carcinogenesis

Tập 56 Số 4

1372-1379

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