Suppressor microRNA-145 Is Epigenetically Regulated by Promoter Hypermethylation in Esophageal Squamous Cell Carcinoma

Anticancer Res. 2015 Sep;35(9):4617-24.

Abstract

Background/aim: DNA methylation is a common epigenetic change in cancer. However, microRNA (miRNA) regulation by epigenetic alteration, especially CpG island hypermethylation, remains poorly understood in esophageal squamous cell carcinoma (ESCC).

Materials and methods: miRNAs which were up-regulated after de-methylation with 5-aza-2'-deoxycytidine (5-AZA) were analyzed using the Human miFinder 384HC miScript miRNA PCR Array. The DNA methylation level was evaluated by bisulfite-pyrosequencing assay.

Results: In two of the cell lines, 20 miRNAs, including miR-145-5p, were found to be up-regulated by more than three-fold after 5-AZA treatment. The miRNA-145 promoter was significantly more hypermethylated in the cancer tissues than in matched normal adjacent esophageal epithelial mucosa (p=0.0042; paired t-test). Moreover, the miRNA-145-5p expression levels were significantly lower in cancerous tissues (p=0.0024).

Conclusion: miRNA-145 expression in ESCC seems to be regulated by hypermethylation of the miRNA-145 promoter region.

Keywords: Cancer epigenetics; DNA methylation; esophageal squamous cell carcinoma; microRNA.

MeSH terms

  • Aged
  • Carcinoma, Squamous Cell / genetics*
  • CpG Islands
  • DNA Methylation / genetics*
  • Disease-Free Survival
  • Epigenesis, Genetic*
  • Esophageal Neoplasms / genetics*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic*

Substances

  • MIRN145 microRNA, human
  • MicroRNAs