dc.creatorLobos González, Lorena
dc.creatorSilva, Verónica
dc.creatorAraya, Mariela
dc.creatorRestovic, Franko
dc.creatorEcheñique, Javiera
dc.creatorOliveira Cruz, Luciana
dc.creatorFitzpatrick, Christopher
dc.creatorBriones, Macarena
dc.creatorVillegas, Jaime
dc.creatorVillota, Claudio
dc.creatorVidaurre, Soledad
dc.creatorBorgna, Vincenzo
dc.creatorSocias, Miguel
dc.creatorValenzuela, Sebastián
dc.creatorLópez, Constanza
dc.creatorSocias, Teresa
dc.creatorVaras, Manuel
dc.creatorDíaz, Jorge
dc.creatorBurzio, Luis O.
dc.creatorBurzio, Verónica A.
dc.date.accessioned2017-11-21T15:07:58Z
dc.date.available2017-11-21T15:07:58Z
dc.date.created2017-11-21T15:07:58Z
dc.date.issued2016
dc.identifierOncotarget, Vol. 7, No. 36 Sept 2016
dc.identifier10.18632/oncotarget.11110
dc.identifierhttps://repositorio.uchile.cl/handle/2250/145708
dc.description.abstractWe reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats. Knockdown of ASncmtRNAs with specific antisense oligonucleotides (ASO) reduces murine melanoma B16F10 cell proliferation and induces apoptosis in vitro through downregulation of pro-survival and metastasis markers, particularly survivin. For in vivo studies, subcutaneous B16F10 melanoma tumors in C57BL/6 mice were treated systemically with specific and control antisense oligonucleotides (ASO). For metastasis studies, tumors were resected, followed by systemic administration of ASOs and the presence of metastatic nodules in lungs and liver was assessed. Treatment with specific ASO inhibited tumor growth and metastasis after primary tumor resection. In a metastasis-only assay, mice inoculated intravenously with cells and treated with the same ASO displayed reduced number and size of melanoma nodules in the lungs, compared to controls. Our results suggest that ASncmtRNAs could be potent targets for melanoma therapy. To our knowledge, the ASncmtRNAs are the first potential non-nuclear targets for melanoma therapy.
dc.languageen
dc.publisherImpact Journals
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.sourceOncotarget
dc.subjectMitochondria
dc.subjectNoncoding RNA
dc.subjectMelanoma
dc.subjectMetastasis
dc.subjectAntisense therapy
dc.titleTargeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors
dc.typeArtículo de revista


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