Critical role of c-Myc in acute myeloid leukemia involving direct regulation of miR-26a and histone methyltransferase EZH2

B Salvatori, I Iosue, N Djodji Damas… - Genes & …, 2011 - journals.sagepub.com
B Salvatori, I Iosue, N Djodji Damas, A Mangiavacchi, S Chiaretti, M Messina, F Padula…
Genes & cancer, 2011journals.sagepub.com
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 …
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 D3 (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.
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