Afficher la notice abrégée

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib

dc.contributor.authorLASSALLE, Sandra
dc.contributor.authorZANGARI, Josephine
dc.contributor.authorPOPA, Alexandra
dc.contributor.authorILIE, Marius
dc.contributor.authorHOFMAN, Veronique
dc.contributor.authorLONG, Elodie
dc.contributor.authorPATEY, Martine
dc.contributor.authorTISSIER, Frederique
dc.contributor.authorBELLEANNEE, Genevieve
dc.contributor.authorTROUETTE, Helene
dc.contributor.authorCATARGI, Bogdan
dc.contributor.authorPEYROTTES, Isabelle
dc.contributor.authorSADOUL, Jean-Louis
dc.contributor.authorBORDONE, Olivier
dc.contributor.authorBONNETAUD, Christelle
dc.contributor.authorBUTORI, Catherine
dc.contributor.authorBOZEC, Alexandre
dc.contributor.authorGUEVARA, Nicolas
dc.contributor.authorSANTINI, Jose
dc.contributor.authorHENAOUI, Imene Sarah
dc.contributor.authorLEMAIRE, Geraldine
dc.contributor.authorBLANK, Olivier
dc.contributor.authorVIELH, Philippe
dc.contributor.authorBARBRY, Pascal
dc.contributor.authorMARI, Bernard
dc.contributor.authorBREST, Patrick
dc.contributor.authorHOFMAN, Paul
dc.date.accessioned2020-09-03T07:56:14Z
dc.date.available2020-09-03T07:56:14Z
dc.date.issued2016
dc.identifier.issn1949-2553
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10852
dc.description.abstractEnIn this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib. Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.
dc.language.isoen
dc.title.enMicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib
dc.typeArticle de revue
dc.identifier.doi10.18632/oncotarget.8458
dc.subject.halChimie/Matériaux
bordeaux.journalOncotarget
bordeaux.page30461-30478
bordeaux.volume7
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.issue21
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=2016&rft.volume=7&rft.issue=21&rft.spage=30461-30478&rft.epage=30461-30478&rft.eissn=1949-2553&rft.issn=1949-2553&rft.au=LASSALLE,%20Sandra&ZANGARI,%20Josephine&POPA,%20Alexandra&ILIE,%20Marius&HOFMAN,%20Veronique&rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée