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Intratumour heterogeneity in microRNAs expression regulates glioblastoma metabolism

Alfardus, Huda; de los Angeles Estevez Cebrero, Maria; Rowlinson, Jonathan; Lourdusamy, Anbarasu; Abdelrazig, Salah; Ortori, Catherine; Grundy, Richard; Kim, Dong-Hyun; McIntyre, Alan; Smith, Stuart

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Huda Alfardus

Maria de los Angeles Estevez Cebrero

Jonathan Rowlinson

Salah Abdelrazig

Catherine Ortori

Professor of Paediatric Neuro-Oncology

Clinical Associate Professor


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.

Journal Article Type Article
Acceptance Date Jul 16, 2021
Online Publication Date Aug 5, 2021
Publication Date Dec 1, 2021
Deposit Date Jul 19, 2021
Publicly Available Date Aug 9, 2021
Journal Scientific Reports
Electronic ISSN 2045-2322
Peer Reviewed Peer Reviewed
Volume 11
Issue 1
Article Number 15908
Public URL
Publisher URL