Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/5384
Título
miR-300 mediates Bmi1 function and regulates differentiation in
primitive cardiac progenitors
Autor(es)
Fecha de publicación
2015
Cita
Cell Death Dis. 2015; 6:e1953
Idioma
Inglés
Tipo de documento
journal article
Resumen
B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family
transcriptional factor critical for self-renewal in many adult stem
cells and human neoplasia. We sought to identify microRNAs regulated by
Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC)
decisions. We found that miR-300, a poorly characterized microRNA
mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by
Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved
stemness signature with a significant increase in Oct4 levels, a
reduction in senescence progression and an enhanced proliferative status
via p19 activation and inhibition of p16 accumulation. Endothelial and
cardiogenic differentiation were clearly compromised by sustained
miR-300 expression. Additionally, RNA and protein analysis revealed a
significant reduction in key cardiac transcription factors, including
Nkx2.5 and Tbx5. Collectively, these results suggest that some functions
attributed to Bmi1 are due to induction of miR-300, which decreases the
cardiogenic differentiation potential of multipotent CPCs in vitro and
promotes self-renewal.
Palabras clave
CELL SELF-RENEWAL | RANDOMIZED PHASE-1 TRIAL | ACTIVATED PROTEIN-KINASE | INTESTINAL STEM-CELLS | MYOCARDIAL-INFARCTION | HEART | PATHWAY | CANCER | CARDIOMYOPATHY | CARDIOMYOCYTES
Versión en línea
DOI
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