Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer

Oncol Rep. 2015 May;33(5):2648-54. doi: 10.3892/or.2015.3870. Epub 2015 Mar 20.

Abstract

Our previous study revealed the potential role of CD147 in human prostate cancer (PCa). Here, we investigated the CD147 promoter methylation status and the correlation with tumorigenicity in human PCa. CD147 mRNA and protein expression levels were both significantly higher in the 4 PCa cell lines, than in the 2 non-tumorigenic benign human prostatic epithelial cell lines (all P<0.01). We showed hypomethylation of promoter regions of CD147 in PCa cell lines with significant CD147 expression as compared to non-tumorigenic benign human prostatic epithelial cell lines slowly expressing CD147. Additionally, the treatment of methylated cell lines with 5-aza-2'-deoxycytidine increased CD147 expression significantly in low-expressing cell lines and also activated the expression of matrix metalloproteinase (MMP)-2, which may be one of the most important downstream targets of CD147. Furthermore, PCa tissues displayed decreased DNA methylation in the promoter region of CD147 compared to the corresponding non-cancerous prostate tissues, and methylation intensity correlated inversely with the CD147 mRNA levels. There was a significant negative correlation between CD147 mRNA levels and the number of methylated sites in PCa tissues (r=-0.467, P<0.01). In conclusion, our data offer convincing evidence for the first time that the DNA promoter hypomethylation of CD147 may be one of the regulatory mechanisms involved in the cancer-related overexpression of CD147 and may play a crucial role in the tumorigenesis of PCa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Basigin / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • DNA Methylation / genetics*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / genetics

Substances

  • BSG protein, human
  • RNA, Messenger
  • Basigin
  • Matrix Metalloproteinase 2