Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism

Abstract 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 i...

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Autores principales:	Huda Alfardus, Maria de los Angeles Estevez-Cebrero, Jonathan Rowlinson, Amna Aboalmaaly, Anbarasu Lourdusamy, Salah Abdelrazig, Catherine Ortori, Richard Grundy, Dong-Hyun Kim, Alan McIntyre, Stuart Smith
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70c79d13cb784e25885855238a077df2
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spelling	oai:doaj.org-article:70c79d13cb784e25885855238a077df22021-12-02T14:53:42ZIntratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism10.1038/s41598-021-95289-92045-2322https://doaj.org/article/70c79d13cb784e25885855238a077df22021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95289-9https://doaj.org/toc/2045-2322Abstract 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.Huda AlfardusMaria de los Angeles Estevez-CebreroJonathan RowlinsonAmna AboalmaalyAnbarasu LourdusamySalah AbdelrazigCatherine OrtoriRichard GrundyDong-Hyun KimAlan McIntyreStuart SmithNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Huda Alfardus Maria de los Angeles Estevez-Cebrero Jonathan Rowlinson Amna Aboalmaaly Anbarasu Lourdusamy Salah Abdelrazig Catherine Ortori Richard Grundy Dong-Hyun Kim Alan McIntyre Stuart Smith Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
description	Abstract 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.
format	article
author	Huda Alfardus Maria de los Angeles Estevez-Cebrero Jonathan Rowlinson Amna Aboalmaaly Anbarasu Lourdusamy Salah Abdelrazig Catherine Ortori Richard Grundy Dong-Hyun Kim Alan McIntyre Stuart Smith
author_facet	Huda Alfardus Maria de los Angeles Estevez-Cebrero Jonathan Rowlinson Amna Aboalmaaly Anbarasu Lourdusamy Salah Abdelrazig Catherine Ortori Richard Grundy Dong-Hyun Kim Alan McIntyre Stuart Smith
author_sort	Huda Alfardus
title	Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism
title_short	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_sort	intratumour heterogeneity in micrornas expression regulates glioblastoma metabolism
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/70c79d13cb784e25885855238a077df2
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Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism

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