dc.contributor.author | Pepe, F | |
dc.contributor.author | Pagotto, S | |
dc.contributor.author | Soliman, S | |
dc.contributor.author | Rossi, C | |
dc.contributor.author | Lanuti, P | |
dc.contributor.author | Braconi, C | |
dc.contributor.author | Mariani-Costantini, R | |
dc.contributor.author | Visone, R | |
dc.contributor.author | Veronese, A | |
dc.date.accessioned | 2019-04-18T09:32:55Z | |
dc.date.issued | 2017-05-08 | |
dc.identifier.citation | Oncogenesis, 2017, 6 (5), pp. e328 - ? | |
dc.identifier.issn | 2157-9024 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3196 | |
dc.identifier.eissn | 2157-9024 | |
dc.identifier.doi | 10.1038/oncsis.2017.35 | |
dc.description.abstract | The 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.format | Electronic | |
dc.format.extent | e328 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Regulation of miR-483-3p by the O-linked N-acetylglucosamine transferase links chemosensitivity to glucose metabolism in liver cancer cells. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-03-29 | |
rioxxterms.versionofrecord | 10.1038/oncsis.2017.35 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-05-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncogenesis | |
pubs.issue | 5 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 6 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
dc.contributor.icrauthor | Braconi, Chiara | |