Afficher la notice abrégée

Modulation of oncogenic miRNA biogenesis using functionalized polyamines

hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorSTAEDEL, Cathy
hal.structure.identifierInstitut de Chimie de Nice [ICN]
dc.contributor.authorTRAN, Thi Phuong Anh
hal.structure.identifierBaRITOn - Bordeaux Research in Translational Oncology
dc.contributor.authorGIRAUD, Julie
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorDARFEUILLE, Fabien
hal.structure.identifierInstitut de Chimie de Nice [ICN]
dc.contributor.authorDI GIORGIO, Audrey
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorTOURASSE, Nicolas J.
hal.structure.identifierBiodiversité, Gènes & Communautés [BioGeCo]
dc.contributor.authorSALIN, Franck
hal.structure.identifierInstitut des Sciences Chimiques de Rennes [ISCR]
dc.contributor.authorURIAC, Philippe
hal.structure.identifierInstitut de Chimie de Nice [ICN]
dc.contributor.authorDUCA, Maria
dc.date.issued2018-12
dc.identifier.issn2045-2322
dc.description.abstractEnMicroRNAs are key factors in the regulation of gene expression and their deregulation has been directly linked to various pathologies such as cancer. The use of small molecules to tackle the overexpression of oncogenic miRNAs has proved its efficacy and holds the promise for therapeutic applications. Here we describe the screening of a 640-compound library and the identification of polyamine derivatives interfering with in vitro Dicer-mediated processing of the oncogenic miR-372 precursor (pre-miR-372). The most active inhibitor is a spermine-amidine conjugate that binds to the pre-miR-372 with a K-D of 0.15 mu M, and inhibits its in vitro processing with a IC50 of 1.06 mu M. The inhibition of miR-372 biogenesis was confirmed in gastric cancer cells overexpressing miR-372 and a specific inhibition of proliferation through de-repression of the tumor suppressor LATS2 protein, a miR-372 target, was observed. This compound modifies the expression of a small set of miRNAs and its selective biological activity has been confirmed in patient-derived ex vivo cultures of gastric carcinoma. Polyamine derivatives are promising starting materials for future studies about the inhibition of oncogenic miRNAs and, to the best of our knowledge, this is the first report about the application of functionalized polyamines as miRNAs interfering agents.
dc.description.sponsorshipCiblage de microARN oncogènes : vers de nouvelles chimiothérapies - ANR-11-JS07-0011
dc.language.isoen
dc.publisherNature Publishing Group
dc.title.enModulation of oncogenic miRNA biogenesis using functionalized polyamines
dc.typeArticle de revue
dc.identifier.doi10.1038/s41598-018-20053-5
dc.subject.halChimie/Chimie thérapeutique
bordeaux.journalScientific Reports
bordeaux.page1667
bordeaux.volume8
bordeaux.issue1
bordeaux.peerReviewedoui
hal.identifierhal-01709540
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-01709540v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Scientific%20Reports&rft.date=2018-12&rft.volume=8&rft.issue=1&rft.spage=1667&rft.epage=1667&rft.eissn=2045-2322&rft.issn=2045-2322&rft.au=STAEDEL,%20Cathy&TRAN,%20Thi%20Phuong%20Anh&GIRAUD,%20Julie&DARFEUILLE,%20Fabien&DI%20GIORGIO,%20Audrey&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