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

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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Submitted on : Tuesday, November 8, 2011 - 5:09:23 PM
Last modification on : Friday, September 17, 2021 - 2:50:09 PM
Long-term archiving on: : Thursday, November 15, 2012 - 11:30:50 AM




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, BioMed Central, 2011, 2 (1), pp.7. ⟨10.1186/1758-907X-2-7⟩. ⟨inserm-00639316⟩



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