A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cells

Leukemia. 2009 May;23(5):856-62. doi: 10.1038/leu.2008.372. Epub 2009 Jan 8.

Abstract

In the acute promyelocytic leukemia (APL) bearing the t(15;17), all-trans-retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. We identified miR-342 as one of the microRNAs (miRNAs) upregulated by ATRA during APL differentiation. This miRNA emerged as a direct transcriptional target of the critical hematopoietic transcription factors PU.1 and interferon regulatory factor (IRF)-1 and IRF-9. IRF-1 maintains miR-342 at low levels, whereas the binding of PU.1 and IRF-9 in the promoter region following retinoic ATRA-mediated differentiation, upregulates miR-342 expression. Moreover, we showed that enforced expression of miR-342 in APL cells stimulated ATRA-induced differentiation. These data identified miR-342 as a new player in the granulocytic differentiation program activated by ATRA in APL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation*
  • Chromatin Immunoprecipitation
  • Granulocytes / cytology*
  • Granulocytes / drug effects
  • Granulocytes / metabolism
  • Humans
  • Immunoblotting
  • Immunophenotyping
  • Interferon Regulatory Factor-1 / genetics*
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / genetics*
  • Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism
  • Introns / genetics
  • Leukemia, Promyelocytic, Acute / genetics*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • MicroRNAs / genetics*
  • MicroRNAs / physiology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Tretinoin / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cell Adhesion Molecules
  • EVL protein, human
  • IRF1 protein, human
  • IRF9 protein, human
  • Interferon Regulatory Factor-1
  • Interferon-Stimulated Gene Factor 3, gamma Subunit
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Tretinoin