Chromatin-modifying drugs induce miRNA-153 expression to suppress Irs-2 in glioblastoma cell lines

Int J Cancer. 2011 Nov 15;129(10):2527-31. doi: 10.1002/ijc.25917. Epub 2011 Apr 1.

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression by inhibiting translation or by promoting mRNA degradation. Previously, we established that microRNA-153 (miR-153) induces apoptosis by downregulating B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia sequence 1 (Mcl-1) protein expression levels in glioblastoma cell line DBTRG-05MG. In our study, we show that ectopic expression of miR-153 also inhibits the protein kinase B (PKB/Akt) pathway via reducing the protein level of insulin receptor substrate-2 (Irs-2). Moreover, simultaneous treatment with the chromatin-modifying drugs 4-phenylbutyric acid and 5-aza-2'-deoxycytidine induces miR-153 expression to suppress Irs-2, Bcl-2 and Mcl-1 expressions, thus downregulating the survival but upregulating the apoptotic pathways, implying that tumor suppressor miR-153 is a dual life and death regulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azacitidine / analogs & derivatives
  • Azacitidine / pharmacology
  • Cell Line, Tumor
  • Chromatin / drug effects
  • Decitabine
  • Glioblastoma / genetics*
  • Humans
  • Insulin Receptor Substrate Proteins / metabolism*
  • MicroRNAs / metabolism*
  • Phenylbutyrates / pharmacology

Substances

  • Chromatin
  • Insulin Receptor Substrate Proteins
  • MIRN153 microRNA, human
  • MicroRNAs
  • Phenylbutyrates
  • Decitabine
  • Azacitidine