miR-29 represses the activities of DNA methyltransferases and DNA demethylases

Int J Mol Sci. 2013 Jul 12;14(7):14647-58. doi: 10.3390/ijms140714647.

Abstract

Members of the microRNA-29 (miR-29) family directly target the DNA methyltransferases, DNMT3A and DNMT3B. Disturbances in the expression levels of miR-29 have been linked to tumorigenesis and tumor aggressiveness. Members of the miR-29 family are currently thought to repress DNA methylation and suppress tumorigenesis by protecting against de novo methylation. Here, we report that members of the miR-29 family repress the activities of DNA methyltransferases and DNA demethylases, which have opposing roles in control of DNA methylation status. Members of the miR-29 family directly inhibited DNA methyltransferases and two major factors involved in DNA demethylation, namely tet methylcytosine dioxygenase 1 (TET1) and thymine DNA glycosylase (TDG). Overexpression of miR-29 upregulated the global DNA methylation level in some cancer cells and downregulated DNA methylation in other cancer cells, suggesting that miR-29 suppresses tumorigenesis by protecting against changes in the existing DNA methylation status rather than by preventing de novo methylation of DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • MicroRNAs / metabolism*
  • Mixed Function Oxygenases
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • Thymine DNA Glycosylase / genetics
  • Thymine DNA Glycosylase / metabolism

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Mixed Function Oxygenases
  • TET1 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Thymine DNA Glycosylase