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: Contribución a la publicaciónArticle

  • 4 Citas

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
Número de edición36
Identificadores de objetos digitales
EstadoPublished - 2016

Huella dactilar

Untranslated RNA
Melanoma
Neoplasm Metastasis
Neoplasms
Antisense RNA
Antisense Oligonucleotides
Lung
Tumor Cell Line
Inbred C57BL Mouse
Down-Regulation
Cell Proliferation
Apoptosis
Liver
In Vitro Techniques

Keywords

    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, Vol. 7, N.º 36, 2016, p. 58331-58350.

    Resultado de la investigación: Contribución a la publicaciónArticle

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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-González and Verónica 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 Sebastián Valenzuela and Constanza Lopez and Teresa Socias and Manuel Varas and Jorge Díaz and Burzio, {Luis O.} and Burzio, {Verónica A.}",
    year = "2016",
    doi = "10.18632/oncotarget.11110",
    volume = "7",
    pages = "58331--58350",
    journal = "Oncotarget",
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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. DOI: 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, 2016, p. 58331-58350.

    Resultado de la investigación: Contribución a la publicaciónArticle

    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

    Y1 - 2016

    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

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    JO - Oncotarget

    T2 - Oncotarget

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    Lobos-González L, Silva V, Araya M, Restovic F, Echenique J, Oliveira-Cruz L y otros. Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. Oncotarget. 2016;7(36):58331-58350. Disponible desde, DOI: 10.18632/oncotarget.11110