Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy

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dc.contributor.authorVidaurre, Soledad
dc.contributor.authorFitzpatrick, Christopher
dc.contributor.authorBurzio, Verónica A.
dc.contributor.authorBriones, Macarena
dc.contributor.authorVillota, Claudio
dc.contributor.authorVillegas, Jaime
dc.contributor.authorEchenique, Javiera
dc.contributor.authorOliveira-Cruz, Luciana
dc.contributor.authorAraya, Mariela
dc.contributor.authorBorgna, Vincenzo
dc.contributor.authorSocías, Teresa
dc.contributor.authorLopez, Constanza
dc.contributor.authorAvila, Rodolfo
dc.contributor.authorBurzio, Luis O.
dc.date.accessioned2023-01-10T15:27:28Z
dc.date.available2023-01-10T15:27:28Z
dc.date.issued2014
dc.description.abstractHallmarks of cancer are fundamental principles involved in cancer progression. We propose an additional generalized hallmark of malignant transformation corresponding to the differential expression of a family of mitochondrial ncRNAs (ncmtRNAs) that comprises sense and antisense members, all of which contain stem-loop structures. Normal proliferating cells express sense (SncmtRNA) and antisense (ASncmtRNA) transcripts. In contrast, the ASncmtRNAs are down-regulated in tumor cells regardless of tissue of origin. Here we show that knockdown of the low copy number of the ASncmtRNAs in several tumor cell lines induces cell death by apoptosis without affecting the viability of normal cells. In addition, knockdown of ASncmtRNAs potentiates apoptotic cell death by inhibiting survivin expression, a member of the inhibitor of apoptosis (IAP) family. Down-regulation of survivin is at the translational level and is probably mediated by microRNAs generated by dicing of the double-stranded stem of the ASncmtRNAs, as suggested by evidence presented here, in which the ASncmtRNAs are bound to Dicer and knockdown of the ASncmtRNAs reduces reporter luciferase activity in a vector carrying the 3′-UTR of survivin mRNA. Taken together, down-regulation of the ASncmtRNAs constitutes a vulnerability or Achilles' heel of cancer cells, suggesting that the ASncmtRNAs are promising targets for cancer therapy. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.es
dc.identifier.doi10.1074/jbc.M114.558841
dc.identifier.issn0021-9258
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/35946
dc.identifier.urihttps://www-sciencedirect-com.recursosbiblioteca.unab.cl/science/article/pii/S002192582037174X?via%3Dihub
dc.language.isoenes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectMitochondrial DNAes
dc.subjectCell Nucleus DNAes
dc.subjectEpigeneticses
dc.titleDown-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapyes
dc.typeArtículoes
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Journal of Biological Chemistry Volume 289, Issue 39, Pages 27182 - 2719826 September 2014
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