ARTÍCULO

EVI1 controls proliferation in acute myeloid leukaemia through modulation of miR-1-2

Autores: Conchillo Armendáriz, Ana; García Garzón, María Antonia; Vázquez Urio, Iria; Maicas Irigarai, Miren; Vicente Vázquez, Carmen; Cristóbal Yoldi, Jon; Marcotegui Arza, Nerea; García-Ortí, L; Bandres Elizalde, Eva María; Calasanz Abinzano, María José; Alonso Roldán, Marta María; Odero de Dios, María Dolores
Título de la revista: BRITISH JOURNAL OF CANCER
ISSN: 0007-0920
Volumen: 103
Número: 8
Páginas: 1292 - 1296
Fecha de publicación: 2010
Resumen:
BAKGROUND: 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.