English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/95785
COMPARTIR / IMPACTO:
Estadísticas
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Título

DGCR8-mediated disruption of miRNA biogenesis induces cellular senescence in primary fibroblasts

AutorGómez-Cabello, Daniel ; Adrados, Isabel; Gamarra, David ; Kobayashi, Hikaru; Takatsu, Yoshihiro; Takatsu, Kyoko; Gil, Jesús; Palmero, Ignacio
Palabras claveMicroRNA
Senescence
Fibroblasts
P53
DGCR8
P21CIP1
Fecha de publicación19-jul-2013
EditorJohn Wiley & Sons
CitaciónAging Cell 12(5): 923- 931 (2013)
ResumenThe regulation of gene expression by microRNAs (miRNAs) is critical for normal development and physiology. Conversely, miRNA function is frequently impaired in cancer, and other pathologies, either by aberrant expression of individual miRNAs or dysregulation of miRNA synthesis. Here, we have investigated the impact of global disruption of miRNA biogenesis in primary fibroblasts of human or murine origin, through the knockdown of DGCR8, an essential mediator of the synthesis of canonical miRNAs. We find that the inactivation of DGCR8 in these cells results in a dramatic antiproliferative response, with the acquisition of a senescent phenotype. Senescence triggered by DGCR8 loss is accompanied by the upregulation of the cell-cycle inhibitor p21CIP1. We further show that a subset of senescence-associated miRNAs with the potential to target p21CIP1 is downregulated during DGCR8-mediated senescence. Interestingly, the antiproliferative response to miRNA biogenesis disruption is retained in human tumor cells, irrespective of p53 status. In summary, our results show that defective synthesis of canonical microRNAs results in cell-cycle arrest and cellular senescence in primary fibroblasts mediated by specific miRNAs, and thus identify global miRNA disruption as a novel senescence trigger. © 2013 The Anatomical Society and John Wiley & Sons Ltd.
Versión del editorhttp://dx.doi.org/10.1111/acel.12117
URIhttp://hdl.handle.net/10261/95785
DOI10.1111/acel.12117
Identificadoresdoi: 10.1111/acel.12117
issn: 1474-9718
Aparece en las colecciones: (CBM) Artículos
(IIBM) Artículos
(CABIMER) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
DGCR8_mediated_disruption_GómezCabello.pdf539,08 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.