title: EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2.
abstract: BACKGROUND
  The EVI1(ecotropic virus integration site 1) gene codes for a zinc-finger transcription factor, whose transcriptional activation leads to a particularly aggressive form of acute myeloid leukaemia (AML). Although, EVI1 interactions with key proteins in hematopoiesis have been previously described, the precise role of this transcription factor in promoting leukaemic transformation is not completely understood. Recent works have identified specific microRNA (miRNA) signatures in different AML subgroups. However, there is no analysis of miRNAs profiles associated with EVI1 overexpression in humans.
  
  
  METHODS
  We performed QT-RT-PCR to assess the expression of 250 miRNAs in cell lines with or without EVI1 overexpression and in patient samples. We used ChIP assays to evaluated the possible binding of EVI1 binding to the putative miRNA promoter. Proliferation of the different cell lines transfected with the anti- or pre-miRs was quantified by MTT.
  
  
  RESULTS
  Our data showed that EVI1 expression was significantly correlated with the expression of miR-1-2 and miR-133-a-1 in established cell lines and in patient samples. ChIP assays confirmed that EVI1 binds directly to the promoter of these two miRNAs. However, only miR-1-2 was involved in abnormal proliferation in EVI1 expressing cell lines.
  
  
  CONCLUSIONS
  Our data showed that EVI1 controls proliferation in AML through modulation of miR-1-2. This study contributes to further understand the transcriptional networks involving transcription factors and miRNAs in AML.
authors.affiliation: Division of Oncology, Center for Applied Medical Research, University of Navarra, Navarra, Pamplona 31008, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Benito
authors.forename: A
authors.initials: A
authors.lastname: Conchillo
authors.forename: M A
authors.initials: MA
authors.lastname: García
authors.forename: I
authors.initials: I
authors.lastname: Vázquez
authors.forename: M
authors.initials: M
authors.lastname: Maicas
authors.forename: C
authors.initials: C
authors.lastname: Vicente
authors.forename: I
authors.initials: I
authors.lastname: Cristobal
authors.forename: N
authors.initials: N
authors.lastname: Marcotegui
authors.forename: L
authors.initials: L
authors.lastname: García-Ortí
authors.forename: E
authors.initials: E
authors.lastname: Bandrés
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: M M
authors.initials: MM
authors.lastname: Alonso
authors.forename: M D
authors.initials: MD
authors.lastname: Odero
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D000074008:MDS1 and EVI1 Complex Locus Protein; D035683:MicroRNAs / Q000235:genetics*; D011485:Protein Binding; D011519:Proto-Oncogenes / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; C553207:MIRN1-2 microRNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors