Helicobacter pylori induces caudal‐type homeobox protein 2 and cyclooxygenase 2 expression by modulating micro RNA s in esophageal epithelial cells

Dysregulation of micro RNA s (mi RNA s) has been linked to virulence factors of Helicobacter pylori . The role of H. pylori in esophageal disease has not been clearly defined. We previously reported that H. pylori esophageal colonization promotes the incidence of Barrett's esophagus and esophageal adenocarcinoma in vivo. Here, we studied the direct effects of H. pylori on the transformation of esophageal epithelial cells, with particular focus on whether H. pylori exerts its effects by modulating mi RNA s and their downstream target genes. The normal human esophageal cell line HET ‐1A was chronically exposed to H. pylori extract and/or acidified deoxycholic acid for up to 36 weeks. The mi RNA profiles of the esophageal epithelial cells associated with H. pylori infection were determined by microarray analysis. We found that chronic H. pylori exposure promoted acidified deoxycholic acid‐induced morphological changes in HET ‐1A cells, along with aberrant overexpression of intestinal metaplasia markers and tumorigenic factors, including caudal‐type homeobox protein 2 ( CDX 2), mucin 2, and cyclooxygenase 2 (COX2). Helicobacter pylori modified the mi RNA profiles of esophageal epithelial cells, particularly aberrant silencing of miR‐212‐3p and miR‐361‐3p. Moreover, in biopsies from Barrett's esophagus patients, esophageal H. pylori colonization was associated with a significant decrease in miR‐212‐3p and miR‐361‐3p expression. Furthermore, we identified COX 2 as a target of miR‐212‐3p, and CDX 2 as a target of miR‐361‐3p. Helicobacter pylori infection of esophageal epithelial cells was associated with mi RNA ‐mediated upregulation of oncoprotein CDX 2 and COX 2. Our observations provide new evidence about the molecular mechanisms underlying the association between H. pylori infection and esophageal carcinogenesis.