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

Lorena Lobos-González, Verónica Silva, Mariela Araya, Franko Restovic, Javiera Echenique, Luciana Oliveira-Cruz, Christopher Fitzpatrick, Macarena Briones, Jaime Villegas, Claudio Villota, Soledad Vidaurre, Vincenzo Borgna, Miguel Socias, Sebastián Valenzuela, Constanza Lopez, Teresa Socias, Manuel Varas, Jorge Díaz, Luis O. Burzio, Verónica A. Burzio

Resultado de la investigación: Article

12 Citas (Scopus)

Resumen

We 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.

Idioma originalEnglish
Páginas (desde-hasta)58331-58350
Número de páginas20
PublicaciónOncotarget
Volumen7
N.º36
DOI
EstadoPublished - 1 ene 2016

Huella dactilar

Untranslated RNA
Antisense RNA
Melanoma
Antisense Oligonucleotides
Neoplasm Metastasis
Survival
Growth
Neoplasms
Lung
Tumor Cell Line
Inbred C57BL Mouse
mitochondrial RNA
Therapeutics
Down-Regulation
Cell Proliferation
Apoptosis
Liver

ASJC Scopus subject areas

  • Oncology

Citar esto

Lobos-González, Lorena ; Silva, Verónica ; Araya, Mariela ; Restovic, Franko ; Echenique, Javiera ; Oliveira-Cruz, Luciana ; Fitzpatrick, Christopher ; Briones, Macarena ; Villegas, Jaime ; Villota, Claudio ; Vidaurre, Soledad ; Borgna, Vincenzo ; Socias, Miguel ; Valenzuela, Sebastián ; Lopez, Constanza ; Socias, Teresa ; Varas, Manuel ; Díaz, Jorge ; Burzio, Luis O. ; Burzio, Verónica A. / Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. En: Oncotarget. 2016 ; Vol. 7, N.º 36. pp. 58331-58350.
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title = "Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors",
abstract = "We 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.",
keywords = "Antisense therapy, Melanoma, Metastasis, Mitochondria, Noncoding RNA",
author = "Lorena Lobos-Gonz{\'a}lez and Ver{\'o}nica Silva and Mariela Araya and Franko Restovic and Javiera Echenique and Luciana Oliveira-Cruz and Christopher Fitzpatrick and Macarena Briones and Jaime Villegas and Claudio Villota and Soledad Vidaurre and Vincenzo Borgna and Miguel Socias and Sebasti{\'a}n Valenzuela and Constanza Lopez and Teresa Socias and Manuel Varas and Jorge D{\'i}az and Burzio, {Luis O.} and Burzio, {Ver{\'o}nica A.}",
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Lobos-González, L, Silva, V, Araya, M, Restovic, F, Echenique, J, Oliveira-Cruz, L, Fitzpatrick, C, Briones, M, Villegas, J, Villota, C, Vidaurre, S, Borgna, V, Socias, M, Valenzuela, S, Lopez, C, Socias, T, Varas, M, Díaz, J, Burzio, LO & Burzio, VA 2016, 'Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors', Oncotarget, vol. 7, n.º 36, pp. 58331-58350. https://doi.org/10.18632/oncotarget.11110

Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. / Lobos-González, Lorena; Silva, Verónica; Araya, Mariela; Restovic, Franko; Echenique, Javiera; Oliveira-Cruz, Luciana; Fitzpatrick, Christopher; Briones, Macarena; Villegas, Jaime; Villota, Claudio; Vidaurre, Soledad; Borgna, Vincenzo; Socias, Miguel; Valenzuela, Sebastián; Lopez, Constanza; Socias, Teresa; Varas, Manuel; Díaz, Jorge; Burzio, Luis O.; Burzio, Verónica A.

En: Oncotarget, Vol. 7, N.º 36, 01.01.2016, p. 58331-58350.

Resultado de la investigación: Article

TY - JOUR

T1 - Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors

AU - Lobos-González, Lorena

AU - Silva, Verónica

AU - Araya, Mariela

AU - Restovic, Franko

AU - Echenique, Javiera

AU - Oliveira-Cruz, Luciana

AU - Fitzpatrick, Christopher

AU - Briones, Macarena

AU - Villegas, Jaime

AU - Villota, Claudio

AU - Vidaurre, Soledad

AU - Borgna, Vincenzo

AU - Socias, Miguel

AU - Valenzuela, Sebastián

AU - Lopez, Constanza

AU - Socias, Teresa

AU - Varas, Manuel

AU - Díaz, Jorge

AU - Burzio, Luis O.

AU - Burzio, Verónica A.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - We 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.

AB - We 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.

KW - Antisense therapy

KW - Melanoma

KW - Metastasis

KW - Mitochondria

KW - Noncoding RNA

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U2 - 10.18632/oncotarget.11110

DO - 10.18632/oncotarget.11110

M3 - Article

VL - 7

SP - 58331

EP - 58350

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 36

ER -