SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme

Abstract Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This...

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Main Authors: D. Mustafov, S. S. Siddiqui, L. Klena, E. Karteris, M. Braoudaki
Format: Article
Language:English
Published: Nature Portfolio 2024-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-55917-6
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author D. Mustafov
S. S. Siddiqui
L. Klena
E. Karteris
M. Braoudaki
author_facet D. Mustafov
S. S. Siddiqui
L. Klena
E. Karteris
M. Braoudaki
author_sort D. Mustafov
collection DOAJ
description Abstract Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.
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spelling doaj.art-31bad21530514ae19760c2d7c1566b682024-03-24T12:16:08ZengNature PortfolioScientific Reports2045-23222024-03-0114111310.1038/s41598-024-55917-6SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiformeD. Mustafov0S. S. Siddiqui1L. Klena2E. Karteris3M. Braoudaki4School of Life and Medical Sciences, University of HertfordshireSchool of Life and Medical Sciences, University of HertfordshireSchool of Life and Medical Sciences, University of HertfordshireCollege of Health, Medicine and Life Sciences, Brunel University LondonSchool of Life and Medical Sciences, University of HertfordshireAbstract Glioblastoma (GBM) is a heterogenous primary brain tumour that is characterised with unfavourable patient prognosis. The identification of biomarkers for managing brain malignancies is of utmost importance. MicroRNAs (miRNAs) are small, non-coding RNAs implicated in cancer development. This study aimed to assess the prognostic significance of miRNAs and their gene targets in GBM. An in silico approach was employed to investigate the differentially expressed miRNAs in GBM. The most dysregulated miRNAs were identified and analysed via Sfold in association with their gene target. The candidate gene was studied via multi-omics approaches, followed by in vitro and in vivo experiments. The in silico analyses revealed that miR-128a and miR-34a were significantly downregulated within GBM. Both miRNAs displayed high binding affinity to the synaptic vesicle glycoprotein 2B (SV2B) 3′ untranslated region (3′UTR). SV2B exhibited upregulation within brain regions with high synaptic activity. Significantly higher SV2B levels were observed in high grade brain malignancies in comparison to their normal counterparts. SV2B expression was observed across the cytoplasm of GBM cells. Our findings underscored the downregulated expression patterns of miR-128a and miR-34a, alongside the upregulation of SV2B in GBM suggesting the importance of the SV2B/miR-34a/miR-128 axis as a potential prognostic approach in GBM management.https://doi.org/10.1038/s41598-024-55917-6
spellingShingle D. Mustafov
S. S. Siddiqui
L. Klena
E. Karteris
M. Braoudaki
SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
Scientific Reports
title SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
title_full SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
title_fullStr SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
title_full_unstemmed SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
title_short SV2B/miR-34a/miR-128 axis as prognostic biomarker in glioblastoma multiforme
title_sort sv2b mir 34a mir 128 axis as prognostic biomarker in glioblastoma multiforme
url https://doi.org/10.1038/s41598-024-55917-6
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