Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of miR-26a and Histone Methyltransferase EZH2
Open Access
- 1 May 2011
- journal article
- Published by SAGE Publications in Genes & Cancer
- Vol. 2 (5), 585-592
- https://doi.org/10.1177/1947601911416357
Abstract
Increased expression or aberrant activation of c-Myc plays an important role in leukemogenesis. Here, we show that in acute myeloid leukemia (AML), c-Myc directly controls the expression of EZH2, a component of the Polycomb repressive complex 2, and miR-26a. miR-26a is downregulated in primary blasts from AML patients and, during myeloid differentiation of AML cells, is induced together with a decrease in c-Myc and Ezh2 levels. Previously, EZH2 was shown to be regulated by miR-26a at the translational levels in lymphomas. However, we demonstrate that in AML, the variation of EZH2 mainly depends on c-Myc transcriptional control. We also show that enforced expression of miR-26a in AML cells is able to inhibit cell cycle progression by downregulating cyclin E2 expression. In addition, increased levels of miR-26a potentiate the antiproliferative effects of 1,25-dihydroxyvitamin D(3) (VitD) and stimulate myeloid differentiation. Our results identify new molecular targets of c-Myc in AML and highlight miR-26a attractiveness as a therapeutic target in leukemiaKeywords
This publication has 30 references indexed in Scilit:
- MiR-26a Inhibits Cell Growth and Tumorigenesis of Nasopharyngeal Carcinoma through Repression of EZH2Cancer Research, 2011
- Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cellsBlood, 2009
- The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivoGenes & Development, 2009
- All-trans retinoic acid induces Thrombospondin-1 expression in acute promyelocytic leukemia cells though down-regulation of its transcription repressor, c-MYC oncoproteinBiochemical and Biophysical Research Communications, 2009
- A new molecular network comprising PU.1, interferon regulatory factor proteins and miR-342 stimulates ATRA-mediated granulocytic differentiation of acute promyelocytic leukemia cellsLeukemia, 2009
- Cooperating gene mutations in acute myeloid leukemia: a review of the literatureLeukemia, 2008
- Widespread microRNA repression by Myc contributes to tumorigenesisNature Genetics, 2007
- A small-molecule c-Myc inhibitor, 10058-F4, induces cell-cycle arrest, apoptosis, and myeloid differentiation of human acute myeloid leukemiaExperimental Hematology, 2006
- Transcriptional regulation and transformation by Myc proteinsNature Reviews Molecular Cell Biology, 2005
- Induction of differentiation in HL60 cells by the reduction of extrachromosomally amplified c-myc.Proceedings of the National Academy of Sciences, 1994