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

doi:10.1038/cddis.2015.10

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

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

25 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
Number of pages	12
Journal	Cell Death & Disease
Volume	6
Issue number	2
DOIs	https://doi.org/10.1038/cddis.2015.10
Publication status	Published - 1 Jan 2015

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Multiple Sclerosis Therapy: Human Pluripotent Stem Cell-derived Neural Progenitor Cells.
Bernard, C., Laslett, A. & O'Brien, C.
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Shu, Runzhe ; Wong, W S Fred ; Ma, Quan-Hong ; Yang, Z Z ; Zhu, H ; Liu, F J ; Wang, Ping ; Ma, Jun ; Yan, S ; Polo, Jose Maria ; Bernard, Claude Charles Andre ; Stanton, Lawrence W ; Dawe, Gavin S ; Xiao, Zhi-cheng. / APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation. In: Cell Death & Disease. 2015 ; Vol. 6, No. 2.

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

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APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation. / Shu, Runzhe; Wong, W S Fred; Ma, Quan-Hong; Yang, Z Z; Zhu, H; Liu, F J; Wang, Ping; Ma, Jun; Yan, S; Polo, Jose Maria ; Bernard, Claude Charles Andre; Stanton, Lawrence W; Dawe, Gavin S; Xiao, Zhi-cheng.

In: Cell Death & Disease, Vol. 6, No. 2, e1651, 01.01.2015.

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

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AU - Shu, Runzhe

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AU - Liu, F J

AU - Wang, Ping

AU - Ma, Jun

AU - Yan, S

AU - Polo, Jose Maria

AU - Bernard, Claude Charles Andre

AU - Stanton, Lawrence W

AU - Dawe, Gavin S

AU - Xiao, Zhi-cheng

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

Abstract

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Projects

Multiple Sclerosis Therapy: Human Pluripotent Stem Cell-derived Neural Progenitor Cells.

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