title: 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.
authors.affiliation: 1] Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia [2] The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650031, China [3] Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Shu
authors.affiliation: 1] Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119077, Singapore [2] Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore [3] Singapore Institute for Neurotechnology (SINAPSE), Singapore 117456, Singapore.
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors.forename: Q H
authors.initials: QH
authors.lastname: Ma
authors.affiliation: 1] Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia [2] The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650031, China.
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Yang
authors.affiliation: 1] Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia [2] The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650031, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 1] Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia [2] College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471000, China.
authors.forename: F J
authors.initials: FJ
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.affiliation: The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650031, China.
authors.forename: S
authors.initials: S
authors.lastname: Yan
authors.affiliation: 1] Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia [2] Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Polo
authors.affiliation: Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: C C A
authors.initials: CC
authors.lastname: Bernard
authors.affiliation: Stem Cell and Developmental Biology Group, Genome Institute of Singapore, Singapore 138672, Singapore.
authors.forename: L W
authors.initials: LW
authors.lastname: Stanton
authors.affiliation: 1] Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119077, Singapore [2] Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore 119077, Singapore [3] Singapore Institute for Neurotechnology (SINAPSE), Singapore 117456, Singapore.
authors.forename: G S
authors.initials: GS
authors.lastname: Dawe
authors.affiliation: 1] Shunxi-Monash Immune Regeneration and Neuroscience Laboratories, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia [2] The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical College, Kunming 650031, China.
authors.forename: Z C
authors.initials: ZC
authors.lastname: Xiao
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; C552243:MIRN663 microRNA, human; D035683:MicroRNAs