title: Helicobacter pylori infection modulates the expression of miRNAs associated with DNA mismatch repair pathway.
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. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, São Francisco University, Bragança Paulista, São Paulo, Brazil.|Women's Integrated Healthcare Center (CAISM), State University of Campinas, (UNICAMP) Campinas, São Paulo, Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Santos
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, São Francisco University, Bragança Paulista, São Paulo, Brazil.
authors.forename: Mitsue T
authors.initials: MT
authors.lastname: Brianti
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, São Francisco University, Bragança Paulista, São Paulo, Brazil.
authors.forename: Victor R
authors.initials: VR
authors.lastname: Almeida
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, São Francisco University, Bragança Paulista, São Paulo, Brazil.
authors.forename: Manoela M
authors.initials: MM
authors.lastname: Ortega
authors.affiliation: Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Fischer
authors.affiliation: Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, München, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.affiliation: Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, and IKERBASQUE, Basque Foundation, Bilbao, Spain.
authors.forename: Ander
authors.initials: A
authors.lastname: Matheu
authors.affiliation: Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, São Francisco University, Bragança Paulista, São Paulo, Brazil.
authors.forename: Marcelo L
authors.initials: ML
authors.lastname: Ribeiro
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D053843:DNA Mismatch Repair; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D013270:Stomach / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology*
chemical_list: D035683:MicroRNAs
keywords: DNA repair; Helicobacter pylori; MMR; gastric cancer