title: Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of miR-26a and Histone Methyltransferase EZH2.
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 leukemia.
authors: Department of Biology and Biotechnology "Charles Darwin", Institute Pasteur Cenci-Bolognetti, Sapienza University of Rome, Rome, Italy.
authors: Beatrice
authors: B
authors: Salvatori
authors: Ilaria
authors: I
authors: Iosue
authors: Nkerorema
authors: N
authors: Djodji Damas
authors: Arianna
authors: A
authors: Mangiavacchi
authors: Sabina
authors: S
authors: Chiaretti
authors: Monica
authors: M
authors: Messina
authors: Fabrizio
authors: F
authors: Padula
authors: Anna
authors: A
authors: Guarini
authors: Irene
authors: I
authors: Bozzoni
authors: Francesco
authors: F
authors: Fazi
authors: Alessandro
authors: A
authors: Fatica