PDCD4 expression inversely correlated with miR-21 levels in gastric cancers

J Cancer Res Clin Oncol. 2012 Apr;138(4):611-9. doi: 10.1007/s00432-011-1140-8. Epub 2012 Jan 3.

Abstract

Purpose: The specific aim of this study was to investigate whether the PDCD4 gene is involved in the development and progression of gastric cancer.

Methods: We examined the genetic and epigenetic alterations of the PDCD4 gene as well as the expression of PDCD4 protein in gastric cancers. The mRNA expression of PDCD4 and miRNA-21 expression were also analyzed using quantitative real-time RT-PCR.

Results: Loss or reduced PDCD4 expression was observed in 79 (36.7%) of 215 gastric cancer specimens. Statistically, altered PDCD4 expression was not associated with the clinicopathological parameters, including tumor differentiation, location, lymph node metastasis and overall survival (P > 0.05). miRNA-21 overexpression was frequently detected in gastric cancers (31 of 46, 67.4%), and there was a significant inverse correlation between miRNA-21 and PDCD4 protein expression (P = 0.029), but not between miRNA-21 and PDCD4 mRNA expression. In genetic analysis, no mutation was detected in the coding region of the PDCD4 gene, and promoter hypermethylation was found in 24 (36.4%) of the 66 gastric cancer samples.

Conclusions: Our data suggest that overexpression of miRNA-21 and reduced or loss of PDCD4 expression may play a role in the development and progression of gastric cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Methylation
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stilbenes / pharmacology
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Tissue Array Analysis

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • MIRN21 microRNA, human
  • MicroRNAs
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Stilbenes
  • Resveratrol