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dc.contributor.authorPepe, F
dc.contributor.authorPagotto, S
dc.contributor.authorSoliman, S
dc.contributor.authorRossi, C
dc.contributor.authorLanuti, P
dc.contributor.authorBraconi, C
dc.contributor.authorMariani-Costantini, R
dc.contributor.authorVisone, R
dc.contributor.authorVeronese, A
dc.date.accessioned2019-04-18T09:32:55Z
dc.date.issued2017-05-08
dc.identifier.citationOncogenesis, 2017, 6 (5), pp. e328 - ?
dc.identifier.issn2157-9024
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3196
dc.identifier.eissn2157-9024
dc.identifier.doi10.1038/oncsis.2017.35
dc.description.abstractThe miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3/PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability. Here we demonstrate that in HepG2 cells, the molecular link between glucose concentration and miR-483-3p expression entails the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), which stabilizes the transcriptional complex at the miR-483 promoter. HepG2 cells showed reduced miR-483-3p expression and increased susceptibility to 5-fluorouracil (5-FU)-induced apoptosis in presence of the inhibitor of glycolysis 2-deoxy-d-glucose (2-DG). However, in vivo experiments showed that HepG2 cells with higher miR-483-3p expression were selected during tumor progression regardless of 5-FU treatment. Furthermore, treatment with 2-DG alone did not significantly reduce HepG2 xenograft load in immunodeficient mice. In conclusion, we show that in HepG2 cells glucose uptake increases the expression of the oncogenic miR-483-3p through the OGT pathway. This suggests that depletion of the miR-483-3p may be a valuable therapeutic approach in liver cancer patients, but the use of inhibitors of glycolysis to achieve this purpose could accelerate the selection of resistant neoplastic cell clones.
dc.formatElectronic
dc.format.extente328 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleRegulation of miR-483-3p by the O-linked N-acetylglucosamine transferase links chemosensitivity to glucose metabolism in liver cancer cells.
dc.typeJournal Article
dcterms.dateAccepted2017-03-29
rioxxterms.versionofrecord10.1038/oncsis.2017.35
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-05-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfOncogenesis
pubs.issue5
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
pubs.publication-statusPublished
pubs.volume6
pubs.embargo.termsNot known
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
dc.contributor.icrauthorBraconi, Chiaraen


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