Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors

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dc.contributor.authorLobos Gonzalez, Lorena
dc.contributor.authorSilva, Veronica
dc.contributor.authorAraya, Mariela
dc.contributor.authorRestovic, Franko
dc.contributor.authorEchenique, Javiera
dc.contributor.authorOliveira Cruz, Luciana
dc.contributor.authorFitzpatrick, Christopher
dc.contributor.authorBriones, Macarena
dc.contributor.authorVillegas, Jaime
dc.contributor.authorVillota, Claudio
dc.contributor.authorVidaurre, Soledad
dc.contributor.authorBorgna, Vincenzo
dc.contributor.authorSocias, Miguel
dc.contributor.authorValenzuela, Sebastian
dc.contributor.authorLopez, Constanza
dc.contributor.authorSocias, Teresa
dc.contributor.authorVaras, Manuel
dc.contributor.authorDiaz, Jorge
dc.contributor.authorBurzio, Luis O.
dc.contributor.authorBurzio, Veronica A.
dc.date.accessioned2024-01-10T13:43:42Z
dc.date.available2024-01-10T13:43:42Z
dc.date.issued2016
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.description.funderCONICYT, Chile
dc.format.extent20 páginas
dc.fuente.origenWOS
dc.identifier.doi10.18632/oncotarget.11110
dc.identifier.eissn1949-2553
dc.identifier.pubmedidMEDLINE:27507060
dc.identifier.urihttps://doi.org/10.18632/oncotarget.11110
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78732
dc.identifier.wosidWOS:000387153200070
dc.information.autorucCiencias Biológicas; Restovic F;S/I;165831
dc.issue.numero36
dc.language.isoen
dc.nota.accesoSin adjunto
dc.pagina.final58350
dc.pagina.inicio58331
dc.publisherIMPACT JOURNALS LLC
dc.revistaONCOTARGET
dc.rightsregistro bibliográfico
dc.subjectmitochondria
dc.subjectnoncoding RNA
dc.subjectmelanoma
dc.subjectmetastasis
dc.subjectantisense therapy
dc.subjectNONCODING RNAS NCRNAS
dc.subjectDOWN-REGULATION
dc.subjectMESENCHYMAL TRANSITION
dc.subjectREPLICATION SLIPPAGE
dc.subjectMICRORNA REGULATION
dc.subjectCANCER PROGRESSION
dc.subjectCUTANEOUS MELANOMA
dc.subjectDNA-POLYMERASES
dc.subjectE-CADHERIN
dc.subjectEXPRESSION
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleTargeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors
dc.typeartículo
dc.volumen7
sipa.codpersvinculados165831
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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