• search hit 8 of 8
Back to Result List

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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-140438
  • 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 cycleBackground 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Cédric Belair, Jessica Baud, Sandrine Chabas, Cynthia M Sharma, Jörg Vogel, Cathy Staedel, Fabien Darfeuille
URN:urn:nbn:de:bvb:20-opus-140438
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):Silence : a Journal of RNA regulation
Year of Completion:2011
Volume:2
Issue:7
Pagenumber:1-16
Source:Silence 2011 2:7.
DOI:https://doi.org/10.1186/1758-907X-2-7
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten
Tag:Helicobacter pylori; MicroRNAs; cell cycle; gastric cancer
Release Date:2018/11/02
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung