microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin

J Biol Chem. 2011 Mar 25;286(12):10725-34. doi: 10.1074/jbc.M110.165654. Epub 2010 Dec 9.

Abstract

microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the up-regulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3'-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins / biosynthesis*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / biosynthesis*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • RNA, Neoplasm / biosynthesis*
  • Survival Rate
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIRN92 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm