miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus

World J Gastroenterol. 2011 Feb 28;17(8):1036-44. doi: 10.3748/wjg.v17.i8.1036.

Abstract

Aim: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma.

Methods: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes.

Results: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenal epithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed significant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05).

Conclusion: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

Keywords: Apoptosis; Barrett’s esophagus; Epithelial to mesenchymal transition; Epithelium; Esophageal adenocarcinoma; Proliferation; miR-200; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Barrett Esophagus / genetics*
  • Barrett Esophagus / pathology*
  • Cell Transformation, Neoplastic
  • Disease Progression*
  • Down-Regulation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology*
  • Gene Regulatory Networks
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1

Substances

  • Homeodomain Proteins
  • MIRN141 microRNA, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Transcription Factors
  • ZEB1 protein, human
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2
  • Zinc Finger E-box-Binding Homeobox 1