title: The microRNA-26a target E2F7 sustains cell proliferation and inhibits monocytic differentiation of acute myeloid leukemia cells.
abstract: Blocks in genetic programs required for terminal myeloid differentiation and aberrant proliferation characterize acute myeloid leukemia (AML) cells. 1,25-Dihydroxy-vitamin D3 (VitD3) arrests proliferation of AML cells and induces their differentiation into mature monocytes. In a previous study, we showed that miR-26a was induced upon VitD3-mediated monocytic differentiation. Here, we identify E2F7 as a novel target of miR-26a. We show that E2F7 significantly promotes cell cycle progression and inhibits monocytic differentiation of AML cells. We also demonstrate that E2F7 binds the cyclin-dependent kinase inhibitor p21(CIP1/WAF1) (cyclin-dependent kinase inhibitor 1A) promoter repressing its expression. Moreover, interfering with E2F7 expression results in inhibition of c-Myc (v-myc myelocytomatosis viral oncogene homolog) transcriptional activity. This leads to the downregulation of c-Myc transcriptional target miR-17-92 cluster, whose expression has a well-defined role in contributing to block monocytic differentiation and sustain AML cell proliferation. Finally, we show that the expression of E2F7 is upregulated in primary blasts from AML patients. Thus, these findings indicate that the newly identified miR-26a target E2F7 might have an important role in monocytic differentiation and leukemogenesis.
authors.affiliation: Department of Biology and Biotechnology 'Charles Darwin' and Institute Pasteur Cenci-Bolognetti, Sapienza University of Rome, Rome, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Salvatori
authors.forename: I
authors.initials: I
authors.lastname: Iosue
authors.forename: A
authors.initials: A
authors.lastname: Mangiavacchi
authors.forename: G
authors.initials: G
authors.lastname: Loddo
authors.forename: F
authors.initials: F
authors.lastname: Padula
authors.forename: S
authors.initials: S
authors.lastname: Chiaretti
authors.forename: N
authors.initials: N
authors.lastname: Peragine
authors.forename: I
authors.initials: I
authors.lastname: Bozzoni
authors.forename: F
authors.initials: F
authors.lastname: Fazi
authors.forename: A
authors.initials: A
authors.lastname: Fatica
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050702:E2F7 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D020298:U937 Cells
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050702:E2F7 Transcription Factor; D035683:MicroRNAs; C528163:MIRN26 microRNA, human