Refine
Has Fulltext
- yes (4)
Is part of the Bibliography
- yes (4)
Year of publication
- 2011 (4) (remove)
Document Type
- Journal article (4)
Language
- English (4)
Keywords
- Chlamydia pneumoniae (1)
- Helicobacter pylori (1)
- MicroRNAs (1)
- RNA (1)
- RNA sequence analyses (1)
- RNS (1)
- SUBSP carotovora (1)
- Salmonella (1)
- bacteria (1)
- campestris PV vesicatoria (1)
- cell cycle (1)
- consesus (1)
- determines pathgenicity (1)
- escherichia coli (1)
- extracellular enzymes (1)
- gastric cancer (1)
- gene expression profiling (1)
- gene-cluster (1)
- genes (1)
- genetic transcription (1)
- genome (1)
- host (organism) (1)
- hypersensitive response (1)
- libraries (1)
- maps (1)
- messanger RNA (1)
- northern blotting (1)
- pathogenetic organism (1)
- pathogenicity (1)
- plants (1)
- ralstonia solanacearum (1)
- regulatory RNA (1)
- secretion systems (1)
- small RNA (1)
- transcription initiation site (1)
- type III protein secretion system complex (1)
- type III secretion system pathways (1)
- untranslated regions (1)
- virulence (1)
- xanthomonas (1)
- xanthomonas campestris (1)
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.