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Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism

While specific microRNA (miRNA) signatures have been identified in glioblastoma (GBM), the intratumour heterogeneity in miRNA expression has not yet been characterised. In this study, we reveal significant alterations in miRNA expression across three GBM tumour regions: the core, rim, and invasive m...

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Autores principales: Alfardus, Huda, de los Angeles Estevez-Cebrero, Maria, Rowlinson, Jonathan, Aboalmaaly, Amna, Lourdusamy, Anbarasu, Abdelrazig, Salah, Ortori, Catherine, Grundy, Richard, Kim, Dong-Hyun, McIntyre, Alan, Smith, Stuart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342598/
https://www.ncbi.nlm.nih.gov/pubmed/34354095
http://dx.doi.org/10.1038/s41598-021-95289-9
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author Alfardus, Huda
de los Angeles Estevez-Cebrero, Maria
Rowlinson, Jonathan
Aboalmaaly, Amna
Lourdusamy, Anbarasu
Abdelrazig, Salah
Ortori, Catherine
Grundy, Richard
Kim, Dong-Hyun
McIntyre, Alan
Smith, Stuart
author_facet Alfardus, Huda
de los Angeles Estevez-Cebrero, Maria
Rowlinson, Jonathan
Aboalmaaly, Amna
Lourdusamy, Anbarasu
Abdelrazig, Salah
Ortori, Catherine
Grundy, Richard
Kim, Dong-Hyun
McIntyre, Alan
Smith, Stuart
author_sort Alfardus, Huda
collection PubMed
description While specific microRNA (miRNA) signatures have been identified in glioblastoma (GBM), the intratumour heterogeneity in miRNA expression has not yet been characterised. In this study, we reveal significant alterations in miRNA expression across three GBM tumour regions: the core, rim, and invasive margin. Our miRNA profiling analysis showed that miR-330-5p and miR-215-5p were upregulated in the invasive margin relative to the core and the rim regions, while miR-619-5p, miR-4440 and miR-4793-3p were downregulated. Functional analysis of newly identified miRNAs suggests their involvement in regulating lipid metabolic pathways. Subsequent liquid chromatography–mass spectrometry (LC–MS) and tandem mass spectroscopy (LC–MS/MS) profiling of the intracellular metabolome and the lipidome of GBM cells with dysregulated miRNA expression confirmed the alteration in the metabolite levels associated with lipid metabolism. The identification of regional miRNA expression signatures may underlie the metabolic heterogeneity within the GBM tumour and understanding this relationship may open new avenues for the GBM treatment.
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spelling pubmed-83425982021-08-10 Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism Alfardus, Huda de los Angeles Estevez-Cebrero, Maria Rowlinson, Jonathan Aboalmaaly, Amna Lourdusamy, Anbarasu Abdelrazig, Salah Ortori, Catherine Grundy, Richard Kim, Dong-Hyun McIntyre, Alan Smith, Stuart Sci Rep Article While specific microRNA (miRNA) signatures have been identified in glioblastoma (GBM), the intratumour heterogeneity in miRNA expression has not yet been characterised. In this study, we reveal significant alterations in miRNA expression across three GBM tumour regions: the core, rim, and invasive margin. Our miRNA profiling analysis showed that miR-330-5p and miR-215-5p were upregulated in the invasive margin relative to the core and the rim regions, while miR-619-5p, miR-4440 and miR-4793-3p were downregulated. Functional analysis of newly identified miRNAs suggests their involvement in regulating lipid metabolic pathways. Subsequent liquid chromatography–mass spectrometry (LC–MS) and tandem mass spectroscopy (LC–MS/MS) profiling of the intracellular metabolome and the lipidome of GBM cells with dysregulated miRNA expression confirmed the alteration in the metabolite levels associated with lipid metabolism. The identification of regional miRNA expression signatures may underlie the metabolic heterogeneity within the GBM tumour and understanding this relationship may open new avenues for the GBM treatment. Nature Publishing Group UK 2021-08-05 /pmc/articles/PMC8342598/ /pubmed/34354095 http://dx.doi.org/10.1038/s41598-021-95289-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Alfardus, Huda
de los Angeles Estevez-Cebrero, Maria
Rowlinson, Jonathan
Aboalmaaly, Amna
Lourdusamy, Anbarasu
Abdelrazig, Salah
Ortori, Catherine
Grundy, Richard
Kim, Dong-Hyun
McIntyre, Alan
Smith, Stuart
Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_full Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_fullStr Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_full_unstemmed Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_short Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_sort intratumour heterogeneity in micrornas expression regulates glioblastoma metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342598/
https://www.ncbi.nlm.nih.gov/pubmed/34354095
http://dx.doi.org/10.1038/s41598-021-95289-9
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