In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization
Author
dc.contributor.author
Varas Godoy, Manuel
Author
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Lladser, Álvaro
Author
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Farfan, Nicole
Author
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Villota, Claudio
Author
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Villegas, Jaime
Author
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Tapia Pineda, Julio
Author
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Burzio, Luis O.
Author
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Burzio, Verónica A.
Author
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Valenzuela, Pablo D. T.
Admission date
dc.date.accessioned
2018-07-25T19:28:17Z
Available date
dc.date.available
2018-07-25T19:28:17Z
Publication date
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2018
Cita de ítem
dc.identifier.citation
Pigment Cell Melanoma Res. 2018;31: 64–72
es_ES
Identifier
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10.1111/pcmr.12615
Identifier
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https://repositorio.uchile.cl/handle/2250/150268
Abstract
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The family of non-coding mitochondrial RNAs (ncmtRNA) is differentially expressed according to proliferative status. Normal proliferating cells express sense (SncmtRNA) and antisense ncmtRNAs (ASncmtRNAs), whereas tumor cells express SncmtRNA and downregulate ASncmtRNAs. Knockdown of ASncmtRNAs with oligonucleotides induces apoptotic cell death of tumor cells, leaving normal cells unaffected, suggesting a potential application for developing a novel cancer therapy. In this study, we knocked down the ASncmtRNAs in melanoma cell lines with a lentiviral-encoded shRNA approach. Transduction with lentiviral constructs targeted to the ASncmtRNAs induced apoptosis in murine B16F10 and human A375 melanoma cells in vitro and significantly retarded B16F10 primary tumor growth in vivo. Moreover, the treatment drastically reduced the number of lung metastatic foci in a tail vein injection assay, compared to controls. These results provide additional proof of concept to the knockdown of ncmtRNAs for cancer therapy and validate lentiviral-shRNA vectors for gene therapy.
es_ES
Patrocinador
dc.description.sponsorship
Universidad Andres Bello
DI11/11
Comision Nacional de Investigacion Cientifica y Tecnologica
Fondecyt 1110845
Fondecyt 11150624
Fondecyt 1140345
Fondecyt 1160889
PFB16