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

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.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.MicroRNAs (miRNAs) are small endogenous non-coding RNAs that have recently emerged along with small interfering RNAs (siRNAs) as key components of the RNA silencing machinery in eukaryotes. Most of them are involved in the tight control of development and cell cycle progression [1,2], and are frequently deregulated in severe pathologies, notably in cancers [3,4]. However, the importance of RNA silencing has been primarily demonstrated in plant defense mechanisms against viruses, where it protects the host by processing long double-stranded (ds)RNAs into siRNAs which, like miRNAs, are loaded onto Argonaute-RNA induced silencing complexes (AGO-RISC) [5] to downregulate gene expression and therefore inhibit viral replication. Recently, evidence has been found to show that miRN