Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells

Cancer Cell. 2006 Jun;9(6):435-43. doi: 10.1016/j.ccr.2006.04.020.

Abstract

Expression profiling of T24 cells revealed that 17 out of 313 human miRNAs were upregulated more than 3-fold by simultaneous treatment with the chromatin-modifying drugs 5-aza-2'-deoxycytidine and 4-phenylbutyric acid. One of these, miR-127, is embedded in a CpG island and is highly induced from its own promoter after treatment. miR-127 is usually expressed as part of a miRNA cluster in normal cells but not in cancer cells, suggesting that it is subject to epigenetic silencing. In addition, the proto-oncogene BCL6, a potential target of miR-127, was translationally downregulated after treatment. These results suggest that DNA demethylation and histone deacetylase inhibition can activate expression of miRNAs that may act as tumor suppressors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Chromatin / metabolism*
  • CpG Islands
  • DNA Methylation / drug effects
  • DNA-Binding Proteins / metabolism*
  • Decitabine
  • Down-Regulation
  • Epigenesis, Genetic
  • Histone Deacetylase Inhibitors
  • Humans
  • MicroRNAs / biosynthesis
  • MicroRNAs / metabolism*
  • Phenylbutyrates / pharmacology
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-6 / metabolism*

Substances

  • BCL6 protein, human
  • Chromatin
  • DNA-Binding Proteins
  • Histone Deacetylase Inhibitors
  • MicroRNAs
  • Phenylbutyrates
  • Proto-Oncogene Proteins c-bcl-6
  • Decitabine
  • 4-phenylbutyric acid
  • Azacitidine