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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Main Authors: 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
Format: article
Language:EN
Published: Nature Portfolio 2021
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Online Access:https://doaj.org/article/70c79d13cb784e25885855238a077df2
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Summary: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.