title: Helicobacter pylori and microRNAs: Relation with innate immunity and progression of preneoplastic conditions.
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.
authors.affiliation: Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Gastroenterology Department, Portuguese Oncology Institute, 4200 Porto, Portugal.
authors.forename: Diogo
authors.initials: D
authors.lastname: Libânio
authors.affiliation: Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Gastroenterology Department, Portuguese Oncology Institute, 4200 Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.affiliation: Diogo Libânio, Mário Dinis-Ribeiro, Pedro Pimentel-Nunes, Gastroenterology Department, Portuguese Oncology Institute, 4200 Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Pimentel-Nunes
keywords: DNA methylation; Gastric cancer; Helicobacter pylori; Immune response; Inflammation; MicroRNA; Preneoplastic conditions; Stomach neoplasms