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dc.contributor.authorCarotenuto, Pen_US
dc.contributor.authorFassan, Men_US
dc.contributor.authorPandolfo, Ren_US
dc.contributor.authorLampis, Aen_US
dc.contributor.authorVicentini, Cen_US
dc.contributor.authorCascione, Len_US
dc.contributor.authorPaulus-Hock, Ven_US
dc.contributor.authorBoulter, Len_US
dc.contributor.authorGuest, Ren_US
dc.contributor.authorQuagliata, Len_US
dc.contributor.authorHahne, JCen_US
dc.contributor.authorRidgway, Ren_US
dc.contributor.authorJamieson, Ten_US
dc.contributor.authorAthineos, Den_US
dc.contributor.authorVeronese, Aen_US
dc.contributor.authorVisone, Ren_US
dc.contributor.authorMurgia, Cen_US
dc.contributor.authorFerrari, Gen_US
dc.contributor.authorGuzzardo, Ven_US
dc.contributor.authorEvans, TRJen_US
dc.contributor.authorMacLeod, Men_US
dc.contributor.authorFeng, GJen_US
dc.contributor.authorDale, Ten_US
dc.contributor.authorNegrini, Men_US
dc.contributor.authorForbes, SJen_US
dc.contributor.authorTerracciano, Len_US
dc.contributor.authorScarpa, Aen_US
dc.contributor.authorPatel, Ten_US
dc.contributor.authorValeri, Nen_US
dc.contributor.authorWorkman, Pen_US
dc.contributor.authorSansom, Oen_US
dc.contributor.authorBraconi, Cen_US
dc.date.accessioned2016-09-28T11:20:26Z
dc.date.issued2017-07en_US
dc.identifier.citationGut, 2017, 66 (7), pp. 1268 - 1277en_US
dc.identifier.issn0017-5749en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/131
dc.identifier.eissn1468-3288en_US
dc.identifier.doi10.1136/gutjnl-2016-312278en_US
dc.description.abstractOBJECTIVE:Transcribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/β-catenin pathway in liver cancer. DESIGN:Hypomorphic Apc mice (Apcfl/fl) and thiocetamide (TAA)-treated rats developed Wnt/β-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation. RESULTS:Overexpression of the T-UCR uc.158- could differentiate Wnt/β-catenin dependent HCC from normal liver and from β-catenin negative diethylnitrosamine (DEN)-induced HCC. uc.158- was overexpressed in human HepG2 versus Huh7 cells in line with activation of the Wnt pathway. In vitro modulation of β-catenin altered uc.158- expression in human malignant hepatocytes. uc.158- expression was increased in CTNNB1-mutated human HCCs compared with non-mutated human HCCs, and in human HCC with nuclear localisation of β-catenin. uc.158- was increased in TAA rat CCA and reduced after treatment with Wnt/β-catenin inhibitors. uc.158- expression was negative in human normal liver and biliary epithelia, while it was increased in human CCA in two different cohorts. Locked nucleic acid-mediated inhibition of uc.158- reduced anchorage cell growth, 3D-spheroid formation and spheroid-based cell migration, and increased apoptosis in HepG2 and SW1 cells. miR-193b was predicted to have binding sites within the uc.158- sequence. Modulation of uc.158- changed miR-193b expression in human malignant hepatocytes. Co-transfection of uc.158- inhibitor and anti-miR-193b rescued the effect of uc.158- inhibition on cell viability. CONCLUSIONS:We showed that uc.158- is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics.en_US
dc.formatPrint-Electronicen_US
dc.format.extent1268 - 1277en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHepatocytesen_US
dc.subjectAnimalsen_US
dc.subjectMice, Knockouten_US
dc.subjectHumansen_US
dc.subjectCarcinoma, Hepatocellularen_US
dc.subjectCholangiocarcinomaen_US
dc.subjectBile Duct Neoplasmsen_US
dc.subjectLiver Neoplasmsen_US
dc.subjectNeoplasms, Experimentalen_US
dc.subjectMicroRNAsen_US
dc.subjectRNA, Untranslateden_US
dc.subjectTransfectionen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectConserved Sequenceen_US
dc.subjectbeta Cateninen_US
dc.subjectWnt Signaling Pathwayen_US
dc.titleWnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-08-17en_US
rioxxterms.versionofrecord10.1136/gutjnl-2016-312278en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2017-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfGuten_US
pubs.issue7en_US
pubs.notesNot knownen_US
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/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.publication-statusPublisheden_US
pubs.volume66en_US
pubs.embargo.termsNot knownen_US
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorBraconi, Chiaraen_US
dc.contributor.icrauthorCarotenuto, Pietroen_US
dc.contributor.icrauthorHahne, Jensen_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorWorkman, Paulen_US
dc.contributor.icrauthorLampis, Andreaen_US


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