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Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades
To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a mi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072706/ https://www.ncbi.nlm.nih.gov/pubmed/29720725 http://dx.doi.org/10.1038/s41388-018-0277-1 |
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author | Li, Ningning Zhang, Ying Sidlauskas, Kastytis Ellis, Matthew Evans, Ian Frankel, Paul Lau, Joanne El-Hassan, Tedani Guglielmi, Loredana Broni, Jessica Richard-Loendt, Angela Brandner, Sebastian |
author_facet | Li, Ningning Zhang, Ying Sidlauskas, Kastytis Ellis, Matthew Evans, Ian Frankel, Paul Lau, Joanne El-Hassan, Tedani Guglielmi, Loredana Broni, Jessica Richard-Loendt, Angela Brandner, Sebastian |
author_sort | Li, Ningning |
collection | PubMed |
description | To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158. GPR158 promotes glioma stem cell differentiation and induces apoptosis and is highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. The correlation of GPR158 expression with molecular subtypes, patient survival and therapy response suggests a possible role of GPR158 as prognostic biomarker in human gliomas. |
format | Online Article Text |
id | pubmed-6072706 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60727062018-08-06 Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades Li, Ningning Zhang, Ying Sidlauskas, Kastytis Ellis, Matthew Evans, Ian Frankel, Paul Lau, Joanne El-Hassan, Tedani Guglielmi, Loredana Broni, Jessica Richard-Loendt, Angela Brandner, Sebastian Oncogene Article To identify biomarkers for glioma growth, invasion and progression, we used a candidate gene approach in mouse models with two complementary brain tumour phenotypes, developing either slow-growing, diffusely infiltrating gliomas or highly proliferative, non-invasive primitive neural tumours. In a microRNA screen we first identified microRNA-449a as most significantly differentially expressed between these two tumour types. miR-449a has a target dependent effect, inhibiting cell growth and migration by downregulation of CCND1 and suppressing neural phenotypes by inhibition of G protein coupled-receptor (GPR) 158. GPR158 promotes glioma stem cell differentiation and induces apoptosis and is highest expressed in the cerebral cortex and in oligodendrogliomas, lower in IDH mutant astrocytomas and lowest in the most malignant form of glioma, IDH wild-type glioblastoma. The correlation of GPR158 expression with molecular subtypes, patient survival and therapy response suggests a possible role of GPR158 as prognostic biomarker in human gliomas. Nature Publishing Group UK 2018-05-03 2018 /pmc/articles/PMC6072706/ /pubmed/29720725 http://dx.doi.org/10.1038/s41388-018-0277-1 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Li, Ningning Zhang, Ying Sidlauskas, Kastytis Ellis, Matthew Evans, Ian Frankel, Paul Lau, Joanne El-Hassan, Tedani Guglielmi, Loredana Broni, Jessica Richard-Loendt, Angela Brandner, Sebastian Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title | Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title_full | Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title_fullStr | Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title_full_unstemmed | Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title_short | Inhibition of GPR158 by microRNA-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
title_sort | inhibition of gpr158 by microrna-449a suppresses neural lineage of glioma stem/progenitor cells and correlates with higher glioma grades |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072706/ https://www.ncbi.nlm.nih.gov/pubmed/29720725 http://dx.doi.org/10.1038/s41388-018-0277-1 |
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