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

doi:10.1038/cddis.2015.10

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

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.

Original language	English
Article number	e1651
Journal	Cell Death and Disease
Volume	6
Issue number	2
DOIs	https://doi.org/10.1038/cddis.2015.10
Publication status	Published - 1 Jan 2015
Externally published	Yes

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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.",

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

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doi = "10.1038/cddis.2015.10",

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T1 - APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation

AU - Shu, R.

AU - Wong, W.

AU - Ma, Q. H.

AU - Yang, Z. Z.

AU - Zhu, H.

AU - Liu, F. J.

AU - Wang, P.

AU - Ma, J.

AU - Yan, S.

AU - Polo, J. M.

AU - Bernard, C. C.A.

AU - Stanton, L. W.

AU - Dawe, G. S.

AU - Xiao, Z. C.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

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VL - 6

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 2

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ER -

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

Abstract

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