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New tumor suppressor microRNAs target glypican-3 in human liver cancer

hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorCARTIER, Flora
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorINDERSIE, Emilie
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorLESJEAN, Sarah
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorCHARPENTIER, Justine
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorHOOKS, Katarzyna B.
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorGHOUSEIN, Amani
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorDESPLAT, Angelique
dc.contributor.authorDUGOT-SENANT, Nathalie
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorTREZEGUET-BUSQUET, Véronique
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorSAGLIOCCO, Francis
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorHAGEDORN, Martin
hal.structure.identifierPhysiopathologie du cancer du foie
dc.contributor.authorGROSSET, Christophe F.
dc.date.accessioned2020-07-09T14:17:06Z
dc.date.available2020-07-09T14:17:06Z
dc.date.issued2017-04-17
dc.identifier.issn1949-2553
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10346
dc.description.abstractEnGlypican-3 (GPC3) is an oncogene, frequently upregulated in liver malignancies such as hepatocellular carcinoma (HCC) and hepatoblastoma and constitutes a potential molecular target for therapy in liver cancer. Using a functional screening system, we identified 10 new microRNAs controlling GPC3 expression in malignant liver cells, five of them e.g. miR-4510, miR-203a-3p, miR-548aa, miR-376b-3p and miR-548v reduce GPC3 expression. These 5 microRNAs were significantly downregulated in tumoral compared to non-tumoral liver and inhibited tumor cell proliferation. Interestingly, miR-4510 inversely correlated with GPC3 mRNA and protein in HCC samples. This microRNA also induced apoptosis of hepatoma cells and blocked tumor growth in vivo in the chick chorioallantoic membrane model. We further show that the tumor suppressive effect of miR-4510 is mediated through direct targeting of GPC3 mRNA and inactivation of Wnt/beta-catenin transcriptional activity and signaling pathway. Moreover, miR-4510 up-regulated the expression of several tumor suppressor genes while reducing the expression of other pro-oncogenes. In summary, we uncovered several new microRNAs targeting the oncogenic functions of GPC3. We provided strong molecular, cellular and in vivo evidences for the tumor suppressive activities of miR-4510 bringing to the fore the potential value of this microRNA in HCC therapy.
dc.title.enNew tumor suppressor microRNAs target glypican-3 in human liver cancer
dc.typeArticle de revue
dc.identifier.doi10.18632/oncotarget.17162
dc.subject.halChimie/Matériaux
bordeaux.journalOncotarget
bordeaux.page41211-41226
bordeaux.volume8
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue25
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Oncotarget&rft.date=2017-04-17&rft.volume=8&rft.issue=25&rft.spage=41211-41226&rft.epage=41211-41226&rft.eissn=1949-2553&rft.issn=1949-2553&rft.au=CARTIER,%20Flora&INDERSIE,%20Emilie&LESJEAN,%20Sarah&CHARPENTIER,%20Justine&HOOKS,%20Katarzyna%20B.&rft.genre=article


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