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

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

来源：Cell Death & Disease, 2015, 6(2): e1651.

DOI：10.1038/cddis.2015.10

• AMYLOID PRECURSOR PROTEIN
• GENE-EXPRESSION
• SIGNALING PATHWAY
• ALZHEIMERS
• MICRORNAS
• BETA
• DISEASE
• TARGET
• AICD
• FE65

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.

• 出版日期2015-2
• 单位河南大学; 昆明医科大学; 苏州大学