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

Soledad Vidaurre, Christopher Fitzpatrick, Verónica A. Burzio, Macarena Briones, Claudio Villota, Jaime Villegas, Javiera Echenique, Luciana Oliveira-Cruz, Mariela Araya, Vincenzo Borgna, Teresa Socías, Constanza Lopez, Rodolfo Avila, Luis O. Burzio

Resultado de la investigación: Research - revisión exhaustivaArticle

  • 19 Citas

Resumen

Hallmarks 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.

IdiomaEnglish
Páginas27182-27198
Número de páginas17
PublicaciónJournal of Biological Chemistry
Volumen289
Número de edición39
DOI
EstadoPublished - 26 sep 2014

Huella dactilar

Untranslated RNA
Down-Regulation
Neoplasms
Therapeutics
Cells
Cell death
Tumors
Apoptosis
Cell Death
3' Untranslated Regions
Luciferases
MicroRNAs
Tissue
Messenger RNA
Tumor Cell Line
Cell Survival

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Citar esto

Vidaurre, Soledad ; Fitzpatrick, Christopher ; Burzio, Verónica A. ; Briones, Macarena ; Villota, Claudio ; Villegas, Jaime ; Echenique, Javiera ; Oliveira-Cruz, Luciana ; Araya, Mariela ; Borgna, Vincenzo ; Socías, Teresa ; Lopez, Constanza ; Avila, Rodolfo ; Burzio, Luis O./ Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy. En: Journal of Biological Chemistry. 2014 ; Vol. 289, N.º 39. pp. 27182-27198
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title = "Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy",
abstract = "Hallmarks 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.",
author = "Soledad Vidaurre and Christopher Fitzpatrick and Burzio, {Verónica A.} and Macarena Briones and Claudio Villota and Jaime Villegas and Javiera Echenique and Luciana Oliveira-Cruz and Mariela Araya and Vincenzo Borgna and Teresa Socías and Constanza Lopez and Rodolfo Avila and Burzio, {Luis O.}",
year = "2014",
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doi = "10.1074/jbc.M114.558841",
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Vidaurre, S, Fitzpatrick, C, Burzio, VA, Briones, M, Villota, C, Villegas, J, Echenique, J, Oliveira-Cruz, L, Araya, M, Borgna, V, Socías, T, Lopez, C, Avila, R & Burzio, LO 2014, 'Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy' Journal of Biological Chemistry, vol. 289, n.º 39, pp. 27182-27198. DOI: 10.1074/jbc.M114.558841

Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy. / Vidaurre, Soledad; Fitzpatrick, Christopher; Burzio, Verónica A.; Briones, Macarena; Villota, Claudio; Villegas, Jaime; Echenique, Javiera; Oliveira-Cruz, Luciana; Araya, Mariela; Borgna, Vincenzo; Socías, Teresa; Lopez, Constanza; Avila, Rodolfo; Burzio, Luis O.

En: Journal of Biological Chemistry, Vol. 289, N.º 39, 26.09.2014, p. 27182-27198.

Resultado de la investigación: Research - revisión exhaustivaArticle

TY - JOUR

T1 - Down-regulation of the antisense mitochondrial non-coding RNAs (ncRNAs) is a unique vulnerability of cancer cells and a potential target for cancer therapy

AU - Vidaurre,Soledad

AU - Fitzpatrick,Christopher

AU - Burzio,Verónica A.

AU - Briones,Macarena

AU - Villota,Claudio

AU - Villegas,Jaime

AU - Echenique,Javiera

AU - Oliveira-Cruz,Luciana

AU - Araya,Mariela

AU - Borgna,Vincenzo

AU - Socías,Teresa

AU - Lopez,Constanza

AU - Avila,Rodolfo

AU - Burzio,Luis O.

PY - 2014/9/26

Y1 - 2014/9/26

N2 - Hallmarks 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.

AB - Hallmarks 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.

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