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      New insights of Helicobacter pylori host-pathogen interactions: The triangle of virulence factors, epigenetic modifications and non-coding RNAs

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          Abstract

          Helicobacter pylori ( H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, MicroRNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.

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          Pathobiology of Helicobacter pylori-Induced Gastric Cancer.

          Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.
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            Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994.

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              Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

              Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.
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                Author and article information

                Contributors
                Journal
                World J Clin Cases
                WJCC
                World Journal of Clinical Cases
                Baishideng Publishing Group Inc
                2307-8960
                16 May 2018
                16 May 2018
                : 6
                : 5
                : 64-73
                Affiliations
                Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Microbiology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran 1316943551, Iran
                Author notes

                Author contributions: All authors contributed to the manuscript.

                Correspondence to: Farzam Vaziri, PhD, Assistant Professor, Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, 12 th Farvardin Ave, Jomhhoori St, Tehran 1316943551, Iran. f_vaziri@ 123456pasteur.ac.ir

                Telephone: +98-21-64112823 Fax: +98-21-64112213

                Article
                jWJCC.v6.i5.pg64
                10.12998/wjcc.v6.i5.64
                5955730
                29774218
                94b32ed9-5665-45ea-8799-39a164975a2d
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                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.

                History
                : 14 January 2018
                : 9 February 2018
                : 7 March 2018
                Categories
                Review

                helicobacter pylori,epigenetic,virulence factor,non-coding rnas,host pathogen interactions

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