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Inhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors

hal.structure.identifierRégulations Naturelles et Artificielles [ARNA]
dc.contributor.authorSTAEDEL, Cathy
hal.structure.identifierInfection à helicobacter, inflammation et cancer
dc.contributor.authorVARON, Christine
hal.structure.identifierInfection à helicobacter, inflammation et cancer
dc.contributor.authorNGUYEN, Phu Hung
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorVIALET, Brune
hal.structure.identifierInfection à helicobacter, inflammation et cancer
dc.contributor.authorCHAMBONNIER, Lucie
hal.structure.identifierService Commun des Animaleries [Bordeaux]
dc.contributor.authorROUSSEAU, Benoît
hal.structure.identifierValidation et identification de nouvelles cibles en oncologie [VINCO]
dc.contributor.authorSOUBEYRAN, Isabelle
hal.structure.identifierInstitut Bergonié [Bordeaux]
dc.contributor.authorEVRARD, Serge
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorCOUILLAUD, Franck
hal.structure.identifierAcides Nucléiques : Régulations Naturelle et Artificielle [ARNA]
dc.contributor.authorDARFEUILLE, Fabien
dc.date.accessioned2021-10-07T16:28:34Z
dc.date.available2021-10-07T16:28:34Z
dc.date.issued2015
dc.identifier.issn2162-2531
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112603
dc.description.abstractEnMicroRNAs regulate eukaryotic gene expression upon pairing onto target mRNAs. This targeting is influenced by the complementarity between the microRNA "seed" sequence at its 5' end and the seed-matching sequences in the mRNA. Here, we assess the efficiency and specificity of 8-mer locked nucleic acid (LNA)-modified oligonucleotides raised against the seeds of miR-372 and miR-373, two embryonic stem cell-specific microRNAs prominently expressed in the human gastric adenocarcinoma AGS cell line. Provided that the pairing is perfect over all the eight nucleotides of the seed and starts at nucleotide 2 or 1 at the microRNA 5' end, these short LNAs inhibit miR-372/373 functions and derepress their common target, the cell cycle regulator LATS2. They decrease cell proliferation in vitro upon either transfection at nanomolar concentrations or unassisted delivery at micromolar concentrations. Subcutaneously delivered LNAs reduce tumor growth of AGS xenografts in mice, upon formation of a stable, specific heteroduplex with the targeted miR-372 and -373 and LATS2 upregulation. Their therapeutic potential is confirmed in fast-growing, miR-372-positive, primary human gastric adenocarcinoma xenografts in mice. Thus, microRNA silencing by 8-mer seed-targeting LNAs appears a valuable approach for both loss-of-function studies aimed at elucidating microRNA functions and for microRNA-based therapeutic strategies.
dc.language.isoen
dc.publisherElsevier
dc.title.enInhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors
dc.typeArticle de revue
dc.identifier.doi10.1038/mtna.2015.18
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalMolecular Therapy - Nucleic Acids
bordeaux.pagee246
bordeaux.volume4
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.issue7
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-02483598
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02483598v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular%20Therapy%20-%20Nucleic%20Acids&rft.date=2015&rft.volume=4&rft.issue=7&rft.spage=e246&rft.epage=e246&rft.eissn=2162-2531&rft.issn=2162-2531&rft.au=STAEDEL,%20Cathy&VARON,%20Christine&NGUYEN,%20Phu%20Hung&VIALET,%20Brune&CHAMBONNIER,%20Lucie&rft.genre=article


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