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. © The Author(s) 2011.
Critical role of c-Myc in acute myeloid leukemia involving direct regulation of miR-26a and histone methyltransferase EZH2 / Salvatori, Beatrice; Iosue', Ilaria; N., Djodji Damas; A., Mangiavacchi; Chiaretti, Sabina; Messina, Monica; Padula, Fabrizio; Guarini, Anna; Bozzoni, Irene; Fazi, Francesco; Fatica, Alessandro. - In: GENES & CANCER. - ISSN 1947-6019. - STAMPA. - 2:5(2011), pp. 585-592. [10.1177/1947601911416357]
Critical role of c-Myc in acute myeloid leukemia involving direct regulation of miR-26a and histone methyltransferase EZH2
SALVATORI, BEATRICE;IOSUE', ILARIA;CHIARETTI, sabina;MESSINA, MONICA;PADULA, Fabrizio;GUARINI, Anna;BOZZONI, Irene;FAZI, Francesco;FATICA, Alessandro
2011
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 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. © The Author(s) 2011.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.