APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.
Cell Death Dis
; 6: e1651, 2015 Feb 19.
Article
em En
| MEDLINE
| ID: mdl-25695604
ABSTRACT
Amyloid precursor protein (APP) is best known for its involvement in the pathogenesis of Alzheimer's disease. We have previously demonstrated that APP intracellular domain (AICD) regulates neurogenesis; however, the mechanisms underlying AICD-mediated regulation of neuronal differentiation are not yet fully characterized. Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, miR-3648 and miR-3687 in human neural stem cells. Functional assays show that AICD negatively modulates neuronal differentiation through miR-663, a primate-specific microRNA. Microarray data further demonstrate that miR-663 suppresses the expression of multiple genes implicated in neurogenesis, including FBXL18 and CDK6. Our results indicate that AICD has a novel role in suppression of neuronal differentiation via transcriptional regulation of miR-663 in human neural stem cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
/
Precursor de Proteína beta-Amiloide
/
MicroRNAs
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Neurônios
Limite:
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2015
Tipo de documento:
Article