dc.contributor.author | Carotenuto, P | |
dc.contributor.author | Fassan, M | |
dc.contributor.author | Pandolfo, R | |
dc.contributor.author | Lampis, A | |
dc.contributor.author | Vicentini, C | |
dc.contributor.author | Cascione, L | |
dc.contributor.author | Paulus-Hock, V | |
dc.contributor.author | Boulter, L | |
dc.contributor.author | Guest, R | |
dc.contributor.author | Quagliata, L | |
dc.contributor.author | Hahne, JC | |
dc.contributor.author | Ridgway, R | |
dc.contributor.author | Jamieson, T | |
dc.contributor.author | Athineos, D | |
dc.contributor.author | Veronese, A | |
dc.contributor.author | Visone, R | |
dc.contributor.author | Murgia, C | |
dc.contributor.author | Ferrari, G | |
dc.contributor.author | Guzzardo, V | |
dc.contributor.author | Evans, TRJ | |
dc.contributor.author | MacLeod, M | |
dc.contributor.author | Feng, GJ | |
dc.contributor.author | Dale, T | |
dc.contributor.author | Negrini, M | |
dc.contributor.author | Forbes, SJ | |
dc.contributor.author | Terracciano, L | |
dc.contributor.author | Scarpa, A | |
dc.contributor.author | Patel, T | |
dc.contributor.author | Valeri, N | |
dc.contributor.author | Workman, P | |
dc.contributor.author | Sansom, O | |
dc.contributor.author | Braconi, C | |
dc.date.accessioned | 2016-09-28T11:20:26Z | |
dc.date.issued | 2016-09-14 | |
dc.identifier.citation | Gut, 2017, 66 (7), pp. 1268 - 1277 | |
dc.identifier.issn | 0017-5749 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/131 | |
dc.identifier.eissn | 1468-3288 | |
dc.identifier.doi | 10.1136/gutjnl-2016-312278 | |
dc.description.abstract | OBJECTIVE: 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. | |
dc.format | Print-Electronic | |
dc.format.extent | 1268 - 1277 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | BMJ PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Hepatocytes | |
dc.subject | Animals | |
dc.subject | Mice, Knockout | |
dc.subject | Humans | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | Cholangiocarcinoma | |
dc.subject | Bile Duct Neoplasms | |
dc.subject | Liver Neoplasms | |
dc.subject | Neoplasms, Experimental | |
dc.subject | MicroRNAs | |
dc.subject | RNA, Untranslated | |
dc.subject | Transfection | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Conserved Sequence | |
dc.subject | beta Catenin | |
dc.subject | Wnt Signaling Pathway | |
dc.title | Wnt signalling modulates transcribed-ultraconserved regions in hepatobiliary cancers. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-08-17 | |
rioxxterms.versionofrecord | 10.1136/gutjnl-2016-312278 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2017-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Gut | |
pubs.issue | 7 | |
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/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics | |
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/Evolutionary Genomics & Modelling | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics | |
pubs.publication-status | Published | |
pubs.volume | 66 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
icr.researchteam | Evolutionary Genomics & Modelling | |
icr.researchteam | Gastrointestinal Cancer Biology and Genomics | |
dc.contributor.icrauthor | Carotenuto, Pietro | |
dc.contributor.icrauthor | Lampis, Andrea | |
dc.contributor.icrauthor | Hahne, Jens | |
dc.contributor.icrauthor | Valeri, Nicola | |
dc.contributor.icrauthor | Workman, Paul | |
dc.contributor.icrauthor | Braconi, Chiara | |