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

Runzhe Shu, W S Fred Wong, Quan-Hong Ma, Z Z Yang, H Zhu, F J Liu, Ping Wang, Jun Ma, S Yan, Jose Maria Polo, Claude Charles Andre Bernard, Lawrence W Stanton, Gavin S Dawe, Zhi-cheng Xiao

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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.
Original languageEnglish
Article numbere1651
Number of pages12
JournalCell Death & Disease
Issue number2
Publication statusPublished - 1 Jan 2015

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