The Roles of miR-26, miR-29, and miR-203 in the Silencing of the Epigenetic Machinery during Melanocyte Transformation

Biomed Res Int. 2015:2015:634749. doi: 10.1155/2015/634749. Epub 2015 Nov 4.

Abstract

The epigenetic marks located throughout the genome exhibit great variation between normal and transformed cancer cells. While normal cells contain hypomethylated CpG islands near gene promoters and hypermethylated repetitive DNA, the opposite pattern is observed in cancer cells. Recently, it has been reported that alteration in the microenvironment of melanocyte cells, such as substrate adhesion blockade, results in the selection of anoikis-resistant cells, which have tumorigenic characteristics. Melanoma cells obtained through this model show an altered epigenetic pattern, which represents one of the first events during the melanocytes malignant transformation. Because microRNAs are involved in controlling components of the epigenetic machinery, the aim of this work was to evaluate the potential association between the expression of miR-203, miR-26, and miR-29 family members and the genes Dnmt3a, Dnmt3b, Mecp2, and Ezh2 during cells transformation. Our results show that microRNAs and their validated or predicted targets are inversely expressed, indicating that these molecules are involved in epigenetic reprogramming. We also show that miR-203 downregulates Dnmt3b in mouse melanocyte cells. In addition, treatment with 5-aza-CdR promotes the expression of miR-26 and miR-29 in a nonmetastatic melanoma cell line. Considering the occurrence of CpG islands near the miR-26 and miR-29 promoters, these data suggest that they might be epigenetically regulated in cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • CpG Islands / drug effects
  • CpG Islands / genetics
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics*
  • Epigenomics / methods
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Silencing / drug effects
  • Gene Silencing / physiology*
  • Melanocytes / drug effects
  • Melanocytes / metabolism*
  • Melanoma / drug therapy
  • Melanoma / genetics
  • Mice
  • MicroRNAs / genetics*
  • Promoter Regions, Genetic / drug effects
  • Promoter Regions, Genetic / genetics

Substances

  • MIRN203 microRNA, mouse
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Mirn26 microRNA, mouse
  • Azacitidine