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

R Shu, W Wong, Q H Ma, Z Z Yang, H Zhu, F J Liu, P Wang, J Ma, S Yan, J M Polo, C C A Bernard, L W Stanton, G S Dawe, Z C Xiao

Cell death & disease 2015

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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.

Citation

R Shu, W Wong, Q H Ma, Z Z Yang, H Zhu, F J Liu, P Wang, J Ma, S Yan, J M Polo, C C A Bernard, L W Stanton, G S Dawe, Z C Xiao. APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation. Cell death & disease. 2015;6:e1651