dc.contributor.author | Lupini, L | |
dc.contributor.author | Pepe, F | |
dc.contributor.author | Ferracin, M | |
dc.contributor.author | Braconi, C | |
dc.contributor.author | Callegari, E | |
dc.contributor.author | Pagotto, S | |
dc.contributor.author | Spizzo, R | |
dc.contributor.author | Zagatti, B | |
dc.contributor.author | Lanuti, P | |
dc.contributor.author | Fornari, F | |
dc.contributor.author | Ghasemi, R | |
dc.contributor.author | Mariani-Costantini, R | |
dc.contributor.author | Bolondi, L | |
dc.contributor.author | Gramantieri, L | |
dc.contributor.author | Calin, GA | |
dc.contributor.author | Sabbioni, S | |
dc.contributor.author | Visone, R | |
dc.contributor.author | Veronese, A | |
dc.contributor.author | Negrini, M | |
dc.date.accessioned | 2019-04-18T09:23:32Z | |
dc.date.issued | 2016-05-24 | |
dc.identifier.citation | Oncotarget, 2016, 7 (21), pp. 31361 - 31371 | |
dc.identifier.issn | 1949-2553 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3194 | |
dc.identifier.eissn | 1949-2553 | |
dc.identifier.doi | 10.18632/oncotarget.8913 | |
dc.description.abstract | The miR-145-5p, which induces TP53-dependent apoptosis, is down-regulated in several tumors, including hepatocellular carcinomas (HCCs), but some HCCs show physiological expression of this miR. Here we demonstrate that in HCC cells carrying wild-type TP53 the steady activation of the miR-145 signaling selects clones resistant to apoptosis via up-regulation of the oncogenic miR-483-3p. Expression of the miR-145-5p and of the miR-483-3p correlated negatively in non-neoplastic liver (n=41; ρ=-0.342, P=0.028), but positively in HCCs (n=21; ρ=0.791, P<0.0001), which we hypothesized to be due to impaired glucose metabolism in HCCs versus normal liver. In fact, when liver cancer cells were grown in low glucose, miR-145-5p lowered miR-483-3p expression, allowing apoptosis, whereas when cells were grown in high glucose the levels of miR-483-3p increased, reducing the apoptotic rate. This indicates that depending on glucose availability the miR-145-5p has double effects on the miR-483-3p, either inhibitory or stimulatory. Moreover, resistance to apoptosis in clones overexpressing both miR-145-5p and miR-483-3p was abrogated by silencing the miR-483-3p. Our data highlight a novel mechanism of resistance to apoptosis in liver cancer cells harbouring wild type TP53 and suggest a potential role of miR-145-5p and miR-483-3p as druggable targets in a subset of HCCs. | |
dc.format | Print | |
dc.format.extent | 31361 - 31371 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | IMPACT JOURNALS LLC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Humans | |
dc.subject | Carcinoma, Hepatocellular | |
dc.subject | Liver Neoplasms | |
dc.subject | Proto-Oncogene Proteins | |
dc.subject | MicroRNAs | |
dc.subject | Oligonucleotide Array Sequence Analysis | |
dc.subject | Apoptosis | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | RNA Interference | |
dc.subject | Mutation | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Tumor Suppressor Protein p53 | |
dc.subject | Apoptosis Regulatory Proteins | |
dc.subject | Hep G2 Cells | |
dc.title | Over-expression of the miR-483-3p overcomes the miR-145/TP53 pro-apoptotic loop in hepatocellular carcinoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-04-10 | |
rioxxterms.versionofrecord | 10.18632/oncotarget.8913 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Oncotarget | |
pubs.issue | 21 | |
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 | 7 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Signal Transduction & Molecular Pharmacology | |
dc.contributor.icrauthor | Braconi, Chiara | |