The role of melatonin in angio-miR-associated inhibition of tumorigenesis and invasion in human glioblastoma tumour spheroids

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorDelen, Emre
dc.contributor.authorDogan, Ayten
dc.date.accessioned2024-06-12T11:02:40Z
dc.date.available2024-06-12T11:02:40Z
dc.date.issued2021
dc.departmentTrakya Üniversitesien_US
dc.description.abstractMicro-RNA (miRNA)-based regulation of hypoxia, angiogenesis and tumour growth provides promising targets for effective therapy in malignant glioblastoma multiforme (GBM). Accumulating evidence suggests a potential role of melatonin in miRNA expression in cancer cells. Despite these findings, the melatonin-miRNA interaction in GBM and the effect of this interaction on GBM tumour development and invasion are not clearly understood. The aim of the present study was to evaluate the effects of melatonin on human GBM tumour spheroid tumorigenesis and invasion in vitro, and to analyse the interaction between 36 angio-miRNAs and the HIF1/VEGF/ MMP9 axis, which is known to be associated with the antitumour effect of melatonin. We found that melatonin is able to selectively induce cell death in single-layer U87-MG cells (a GBM cell line) in a dose- and time-dependent manner, as characterized by MTT assay. The use of tumour spheroids and a Matrigel invasion assay revealed that melatonin impairs tumorigenesis, and it significantly reduced both the tumour spheroid area and invasion rate, especially at the 0.5 mM and 1 mM concentrations. This inhibition was accompanied by strong reductions in hypoxia-inducible factor 1-alpha (HIF1-alpha) and vascular endothelial growth factor (VEGF) gene expression and protein levels in GBM tumour spheroids. In addition, melatonin significantly reduced the relative gene expression and protein levels of matrix metalloproteinase-9 (MMP-9). This study revealed that six differentially expressed angio-miRs (miR-15b, miR-18a-5p, miR-23a-3p, miR-92a-3p, miR-130a-5p, miR-200b-3p) may play important roles in GBM tumorigenesis and invasion, and all respond to melatonin therapy. Our results suggest that melatonin inhibits tumorigenesis and invasion of human GBM tumour spheroids, possibly by suppressing HIF1 alpha/VEGF/MMP9 signalling via regulation of angio-miRNAs.en_US
dc.description.sponsorshipTrakya University Scientific Research Fund [TUBAP 2017/217]en_US
dc.description.sponsorshipThis study was supported by the Trakya University Scientific Research Fund (TUBAP 2017/217) . We are particularly grateful to Dr. Esin Akbay Cetin who provided brain tumour cell line. We also thank Ayse Kardelen Kurtdere and Tourkian CHASAN for their technical assistance on C6 and T98G studies.en_US
dc.identifier.doi10.1016/j.tice.2021.101617
dc.identifier.issn0040-8166
dc.identifier.pmid34418770en_US
dc.identifier.scopus2-s2.0-85112739860en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1016/j.tice.2021.101617
dc.identifier.urihttps://hdl.handle.net/20.500.14551/21378
dc.identifier.volume73en_US
dc.identifier.wosWOS:000744261900006en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherChurchill Livingstoneen_US
dc.relation.ispartofTissue & Cellen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectGlioblastoma Multiformeen_US
dc.subjectHypoxiaen_US
dc.subjectAngiogenesisen_US
dc.subjectMicrornaen_US
dc.subjectMelatoninen_US
dc.subjectEndothelial Growth-Factoren_US
dc.subjectMatrix Metalloproteinasesen_US
dc.subjectCell-Proliferationen_US
dc.subjectGliomaen_US
dc.subjectExpressionen_US
dc.subjectMicrornaen_US
dc.subjectHypoxiaen_US
dc.subjectAngiogenesisen_US
dc.subjectIdentificationen_US
dc.subjectMigrationen_US
dc.titleThe role of melatonin in angio-miR-associated inhibition of tumorigenesis and invasion in human glioblastoma tumour spheroidsen_US
dc.typeArticleen_US

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