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Journal Articles Silence Year : 2011

Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression.

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Abstract

UNLABELLED: ABSTRACT: BACKGROUND: MicroRNAs, post-transcriptional regulators of eukaryotic gene expression, are implicated in host defense against pathogens. Viruses and bacteria have evolved strategies that suppress microRNA functions, resulting in a sustainable infection. In this work we report that Helicobacter pylori, a human stomach-colonizing bacterium responsible for severe gastric inflammatory diseases and gastric cancers, downregulates an embryonic stem cell microRNA cluster in proliferating gastric epithelial cells to achieve cell cycle arrest. RESULTS: Using a deep sequencing approach in the AGS cell line, a widely used cell culture model to recapitulate early events of H. pylori infection of gastric mucosa, we reveal that hsa-miR-372 is the most abundant microRNA expressed in this cell line, where, together with hsa-miR-373, it promotes cell proliferation by silencing large tumor suppressor homolog 2 (LATS2) gene expression. Shortly after H. pylori infection, miR-372 and miR-373 synthesis is highly inhibited, leading to the post-transcriptional release of LATS2 expression and thus, to a cell cycle arrest at the G1/S transition. This downregulation of a specific cell-cycle-regulating microRNA is dependent on the translocation of the bacterial effector CagA into the host cells, a mechanism highly associated with the development of severe atrophic gastritis and intestinal-type gastric carcinoma. CONCLUSIONS: These data constitute a novel example of host-pathogen interplay involving microRNAs, and unveil the couple LATS2/miR-372 and miR-373 as an unexpected mechanism in infection-induced cell cycle arrest in proliferating gastric cells, which may be relevant in inhibition of gastric epithelium renewal, a major host defense mechanism against bacterial infections.
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Dates and versions

inserm-00639316 , version 1 (08-11-2011)

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Cédric Belair, Jessica Baud, Sandrine Chabas, Cynthia Sharma, Jörg Vogel, et al.. Helicobacter pylori interferes with an embryonic stem cell micro RNA cluster to block cell cycle progression.. Silence, 2011, 2 (1), pp.7. ⟨10.1186/1758-907X-2-7⟩. ⟨inserm-00639316⟩

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