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Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression

Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. Durin...

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Autores principales: Xiong, Anqi, Roy, Ananya, Spyrou, Argyris, Weishaupt, Holger, Marinescu, Voichita D., Olofsson, Tommie, Hermanson, Ola, Swartling, Fredrik J., Forsberg-Nilsson, Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352854/
https://www.ncbi.nlm.nih.gov/pubmed/32517178
http://dx.doi.org/10.3390/cancers12061483
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author Xiong, Anqi
Roy, Ananya
Spyrou, Argyris
Weishaupt, Holger
Marinescu, Voichita D.
Olofsson, Tommie
Hermanson, Ola
Swartling, Fredrik J.
Forsberg-Nilsson, Karin
author_facet Xiong, Anqi
Roy, Ananya
Spyrou, Argyris
Weishaupt, Holger
Marinescu, Voichita D.
Olofsson, Tommie
Hermanson, Ola
Swartling, Fredrik J.
Forsberg-Nilsson, Karin
author_sort Xiong, Anqi
collection PubMed
description Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. During mouse brain development, NRBP2 is expressed in the cerebellum, and in the adult brain, mainly confined to specific neuronal populations. To study the role of NRBP2 in brain tumors, we stained a brain tumor tissue array for NRPB2, and find its expression to be low, or absent, in a majority of the tumors. This includes medulloblastoma (MB), a pediatric tumor of the cerebellum. Using database mining of published MB data sets, we also find that NRBP2 is expressed at a lower level in MB than in the normal cerebellum. Recent studies indicate that MB exhibits frequent epigenetic alternations and we therefore treated MB cell lines with drugs inhibiting DNA methylation or histone deacetylation, which leads to an upregulation of NRBP2 mRNA expression, showing that it is under epigenetic regulation in cultured MB cells. Furthermore, forced overexpression of NRBP2 in MB cell lines causes a dramatic decrease in cell numbers, increased cell death, impaired cell migration and inhibited cell invasion in vitro. Taken together, our data indicate that downregulation of NRBP2 may be a feature by which MB cells escape growth regulation.
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spelling pubmed-73528542020-07-15 Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression Xiong, Anqi Roy, Ananya Spyrou, Argyris Weishaupt, Holger Marinescu, Voichita D. Olofsson, Tommie Hermanson, Ola Swartling, Fredrik J. Forsberg-Nilsson, Karin Cancers (Basel) Article Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. During mouse brain development, NRBP2 is expressed in the cerebellum, and in the adult brain, mainly confined to specific neuronal populations. To study the role of NRBP2 in brain tumors, we stained a brain tumor tissue array for NRPB2, and find its expression to be low, or absent, in a majority of the tumors. This includes medulloblastoma (MB), a pediatric tumor of the cerebellum. Using database mining of published MB data sets, we also find that NRBP2 is expressed at a lower level in MB than in the normal cerebellum. Recent studies indicate that MB exhibits frequent epigenetic alternations and we therefore treated MB cell lines with drugs inhibiting DNA methylation or histone deacetylation, which leads to an upregulation of NRBP2 mRNA expression, showing that it is under epigenetic regulation in cultured MB cells. Furthermore, forced overexpression of NRBP2 in MB cell lines causes a dramatic decrease in cell numbers, increased cell death, impaired cell migration and inhibited cell invasion in vitro. Taken together, our data indicate that downregulation of NRBP2 may be a feature by which MB cells escape growth regulation. MDPI 2020-06-06 /pmc/articles/PMC7352854/ /pubmed/32517178 http://dx.doi.org/10.3390/cancers12061483 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiong, Anqi
Roy, Ananya
Spyrou, Argyris
Weishaupt, Holger
Marinescu, Voichita D.
Olofsson, Tommie
Hermanson, Ola
Swartling, Fredrik J.
Forsberg-Nilsson, Karin
Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title_full Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title_fullStr Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title_full_unstemmed Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title_short Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression
title_sort nuclear receptor binding protein 2 is downregulated in medulloblastoma, and reduces tumor cell survival upon overexpression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352854/
https://www.ncbi.nlm.nih.gov/pubmed/32517178
http://dx.doi.org/10.3390/cancers12061483
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