Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of miR-26a and Histone Methyltransferase EZH2

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 blast...

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Published in:Genes & cancer 2011-05, Vol.2 (5), p.585-592
Main Authors: Salvatori, Beatrice, Iosue, Ilaria, Djodji Damas, Nkerorema, Mangiavacchi, Arianna, Chiaretti, Sabina, Messina, Monica, Padula, Fabrizio, Guarini, Anna, Bozzoni, Irene, Fazi, Francesco, Fatica, Alessandro
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Cancer
Life Sciences
Short Reports
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Summary: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 leukemia.
ISSN:1947-6019
1947-6027
DOI:10.1177/1947601911416357