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APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.


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.

SUBMITTER: Shu R 

PROVIDER: S-EPMC4669786 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation.

Shu R R   Wong W W   Ma Q H QH   Yang Z Z ZZ   Zhu H H   Liu F J FJ   Wang P P   Ma J J   Yan S S   Polo J M JM   Bernard C C A CC   Stanton L W LW   Dawe G S GS   Xiao Z C ZC  

Cell death & disease 20150219


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 tran  ...[more]

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