DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis

Eur J Med Res. 2012 May 18;17(1):12. doi: 10.1186/2047-783X-17-12.

Abstract

Background: Accumulated evidence reveals that cyclooxygenase-2 (COX-2) was overexpressed in eutopic endometrium of endometriosis, which may play a critical role in the pathogenesis of endometriosis. However, few studies have been performed to explore the molecular mechanisms underlying the abnormal high expression of COX-2 in endometriosis. Considering the fact that a number of recent studies have shown DNA methylation affecting some genes in endometriosis, the present study was therefore aimed to determine whether the observed high expression COX-2 in endometriosis is caused by the hypomethylation of CpG island within the promoter of this gene.

Methods: The endometrial tissues were collected from 60 women with endometriosis (endometriosis group) and 20 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation specific PCR. Quantitative real-time RT-PCR was performed to measure COX-2 mRNA level in endometrial tissues.

Results: The frequency of promoter hypermethylation of COX-2 was lower in eutopic endometrium of the endometriosis group (41.7%) than that in the control group (75.0%), P < 0.05. COX-2 mRNA level in the eutopic endometrium of the endometriosis group was 2.61-fold higher than that in the control group (P < 0.01). COX-2 mRNA level in unmethylated endometrium of the endometriosis group or the control group was 2.39-fold and 2.66-fold, respectively, higher than that in the methylated endometrium of the same group (P < 0.01).

Conclusions: The hypomethylation within the promoter of COX-2 may be responsible for the elevated gene expression in eutopic endometrium of endometriosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • Case-Control Studies
  • CpG Islands
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • DNA Methylation*
  • Endometriosis / genetics*
  • Endometriosis / pathology
  • Endometrium / metabolism
  • Endometrium / pathology*
  • Epigenesis, Genetic
  • Female
  • Humans
  • Middle Aged
  • Promoter Regions, Genetic*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Up-Regulation

Substances

  • CEBPD protein, human
  • RNA, Messenger
  • CCAAT-Enhancer-Binding Protein-delta
  • Cyclooxygenase 2
  • PTGS2 protein, human