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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 10, 2015; 6(5): 111-132
Published online Oct 10, 2015. doi: 10.5306/wjco.v6.i5.111
Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions
Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes
Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Gastroenterology Department, Portuguese Oncology Institute, 4200 Porto, Portugal
Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Center for Health Technology and Services Resarch, Faculty of Medicine University of Porto, 4200 Porto, Portugal
Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Department of Health Information and Decision Sciences, Faculty of Medicine University of Porto, 4200 Porto, Portugal
Pedro Pimentel-Nunes, Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine University of Porto, 4200 Porto, Portugal
Author contributions: Libânio D designed the review, conducted the search and wrote the manuscript; Dinis-Ribeiro M contributed to study conception, interpretation of data, manuscript writing and revised the manuscript; Pimentel-Nunes P contributed to study conception, interpretation of data, manuscript writing and revised the manuscript; all authors aproved the final version of the manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest of any kind.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Diogo Libânio, MD, Gastroenterology Department, Portuguese Oncology Institute, Rua Dr. António Bernardino de Almeida, 4200 Porto, Portugal. diogolibaniomonteiro@gmail.com
Telephone: +351-225-84000 Fax: +351-225-84001
Received: March 29, 2015
Peer-review started: March 29, 2015
First decision: June 3, 2015
Revised: June 22, 2015
Accepted: August 4, 2015
Article in press: August 7, 2015
Published online: October 10, 2015
Processing time: 198 Days and 0.5 Hours
Abstract

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori (H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. MicroRNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify microRNA expression in the gastric mucosa and microRNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. MicroRNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor microRNAs. Furthermore, microRNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, microRNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each microRNA can control the expression of hundreds to thousands of genes, knowledge of microRNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of microRNAs in H. pylori gastric carcinogenesis, identifying the microRNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

Keywords: Helicobacter pylori, MicroRNA, Gastric cancer, Inflammation, DNA methylation, Preneoplastic conditions, Stomach neoplasms, Immune response

Core tip:Helicobacter pylori (H. pylori) are involved in the progression of gastric preneoplastic conditions and gastric carcinogenesis although the clear genetic and molecular mechanisms are not completely clear. MicroRNAs may have an important role in the development of H. pylori mediated pathology since they can alter the expression of hundreds to thousands of genes. In this article we present a comprehensive review about the microRNAs that are altered in H. pylori infection and the biological consequences of this alteration, linking the inflammatory and immune host response with the progression of preneoplastic conditions and gastric carcinogenesis.