Inhibition of the Invasion of Human Glioblastoma U87 Cell Line by Ruxolitinib: A Molecular Player of miR-17 and miR-20a Regulating JAK/STAT Pathway

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dc.authoridDoganlar, Zeynep Banu/0000-0002-1365-9897
dc.authoriddelen, ozlem/0000-0001-5652-2658
dc.authoridDoganlar, Oguzhan/0000-0003-2654-7269
dc.authorwosidDoganlar, Zeynep Banu/B-4845-2008
dc.authorwosidDoğanlar, Oğuzhan/A-2315-2019
dc.contributor.authorDelen, Emre
dc.contributor.authorDoganlar, Oguzhan
dc.contributor.authorDoganlar, Zeynep Banu
dc.contributor.authorDelen, Ozlem
dc.date.accessioned2024-06-12T10:51:42Z
dc.date.available2024-06-12T10:51:42Z
dc.date.issued2020
dc.departmentTrakya Üniversitesien_US
dc.description33rd National Scientific Congress of the Turkish-Neurosurgical-Society -- APR 11-14, 2019 -- Antaly, TURKEYen_US
dc.description.abstractAIM: To determine the interaction between ruxolitinib, JAK/STAT signalling, and two angio-microRNAs (miRs) to expose potential target molecules in the inhibition of glioblastoma invasion. MATERIAL and METHODS: The invasion properties of glioblastoma were analyzed using a cancer cell spheroid invasion assay. Following treatment of 195 nM ruxolitinib, the relative expression levels of miR-17 and miR-20a and genes of IL-6/JAK/STAT3 receptor signaling belonging to the JAK/STAT pathway were measured by qRT-PCR in treated and untreated three-dimensional tumor spheres of U87 cells. RESULTS: Our results indicated that a therapeutic dose of ruxolitinib (195 nM) significantly increased miR-17 and miR-20a expression. Ruxolitinib treatment resulted in the production of IL-6 and active formation of IL-6 receptor complex for the subsequent activation of the IL-6R/JAK2/STAT3 axis. However, ruxolitinib treatment significantly decreased the expression of JAK2 and PI3K. Pearson correlation analyses revealed a strong negative correlation of miR-17 with JAK2, STAT3, and PI3K expressions, and also miR-20a has a negative correlation with expression levels of JAK2 and PI3K. The only positive correlation was found to be between miR-20a and IL-6, gp130 expressions. CONCLUSION: The specific JAK2 inhibitor ruxolitinib plays an important role in glioblastoma angiogenesis biology via inhibiting IL-6 receptor-dependent JAK/STAT signaling. Additionally, both miR-17a-3p and miR-20a overexpression induced by ruxolitinib treatment may be playing a major role in downregulated JAK2, STAT3, and PI3K proteins. Our results suggest that miR-17-3p and miR-20a-5p may serve as new therapeutic targets for the treatment of glioblastoma.en_US
dc.description.sponsorshipTurkish Neurosurg Socen_US
dc.description.sponsorshipTrakya University Scientific Research [TUBAP-2018/155]en_US
dc.description.sponsorshipThis study was funded by the Trakya University Scientific Research (TUBAP-2018/155).en_US
dc.identifier.doi10.5137/1019-5149.JTN.26122-19.1
dc.identifier.endpage189en_US
dc.identifier.issn1019-5149
dc.identifier.issue2en_US
dc.identifier.pmid31452174en_US
dc.identifier.scopus2-s2.0-85081942811en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage182en_US
dc.identifier.trdizinid356654en_US
dc.identifier.urihttps://doi.org/10.5137/1019-5149.JTN.26122-19.1
dc.identifier.urihttps://search.trdizin.gov.tr/yayin/detay/356654
dc.identifier.urihttps://hdl.handle.net/20.500.14551/18458
dc.identifier.volume30en_US
dc.identifier.wosWOS:000519545800005en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakTR-Dizinen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTurkish Neurosurgical Socen_US
dc.relation.ispartofTurkish Neurosurgeryen_US
dc.relation.publicationcategoryKonferans Öğesi - Uluslararası - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectAngiogenesis Inhibitorsen_US
dc.subjectDrug Effectsen_US
dc.subjectGlioblastomaen_US
dc.subjectInvasionen_US
dc.subjectRuxolitiniben_US
dc.subjectJAK/STAT Signaling Pathwayen_US
dc.subjectMicrornasen_US
dc.subjectMolecular Targeted Therapyen_US
dc.subjectMicrornas Confers Tumorigenicityen_US
dc.subjectStat3en_US
dc.subjectBiomarkersen_US
dc.subjectApoptosisen_US
dc.subjectTherapyen_US
dc.subjectClusteren_US
dc.subjectIl-6en_US
dc.titleInhibition of the Invasion of Human Glioblastoma U87 Cell Line by Ruxolitinib: A Molecular Player of miR-17 and miR-20a Regulating JAK/STAT Pathwayen_US
dc.typeConference Objecten_US

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