Helicobacter pylori-induced post-transcriptional regulation of H,K-ATPase α subunit gene expression by miRNA.

Helicobacter pylori-induced post-transcriptional regulation of H,K-ATPase α subunit gene expression by miRNA. Am J Physiol Gastrointest Liver Physiol. 2014 Feb 6; Authors: Zhang YM, Noto JM, Hammond CE, Barth JL, Argraves WS, Backert S, Peek RM, Smolka AJ Abstract Acute H. pylori infection of gastric epithelial cells induces CagA oncoprotein- and peptidoglycan (SLT)-dependent mobilization of NF-κB p50 homodimers that bind to H,K-ATPase α subunit (HKα) promoter and repress HKα gene transcription. This process may facilitate gastric H. pylori colonization by induction of transient hypochlorhydria. We hypothesized that H. pylori also regulates HKα expression post-transcriptionally by miRNA interaction with HKα mRNA. In silico analysis of HKα 3' untranslated region (UTR) identified miR-1289 as a highly-conserved putative HKα-regulatory miRNA. H. pylori infection of AGS cells transfected with HKα 3' UTR-Luc reporter construct repressed luciferase activity by 70%, while ΔcagA or Δslt H. pylori infections partially abrogated repression. Transfection of AGS cells expressing HKα 3' UTR-Luc construct with an oligoribonucleotide mimetic of miR-1289 induced maximal repression (54%) of UTR activity within 30 min; UTR activity was unchanged by non-targeting siRNA transfection. Gastric biopsies from patients infected with cagA(+) H. pylori showed a significant increase in miR-1289 expression compared to uninfected patients or those infected with...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research