In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization

Manuel Varas-Godoy, Alvaro Lladser, Nicole Farfan, Claudio Villota, Jaime Villegas, Julio C. Tapia, Luis O. Burzio, Veronica A. Burzio, Pablo D.T. Valenzuela

Resultado de la investigación: Article

2 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)64-72
Número de páginas9
PublicaciónPigment Cell and Melanoma Research
Volumen31
N.º1
DOI
EstadoAccepted/In press - 1 ene 2017

Huella dactilar

Antisense RNA
Untranslated RNA
Small Interfering RNA
Tumors
Melanoma
Cells
Lung
Growth
Gene therapy
Neoplasms
Cell death
Oligonucleotides
Assays
Apoptosis
Genetic Therapy
Tail
Veins
Cell Death
Therapeutics
Down-Regulation

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

Citar esto

Varas-Godoy, Manuel ; Lladser, Alvaro ; Farfan, Nicole ; Villota, Claudio ; Villegas, Jaime ; Tapia, Julio C. ; Burzio, Luis O. ; Burzio, Veronica A. ; Valenzuela, Pablo D.T. / In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization. En: Pigment Cell and Melanoma Research. 2017 ; Vol. 31, N.º 1. pp. 64-72.
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abstract = "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.",
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In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization. / Varas-Godoy, Manuel; Lladser, Alvaro; Farfan, Nicole; Villota, Claudio; Villegas, Jaime; Tapia, Julio C.; Burzio, Luis O.; Burzio, Veronica A.; Valenzuela, Pablo D.T.

En: Pigment Cell and Melanoma Research, Vol. 31, N.º 1, 01.01.2017, p. 64-72.

Resultado de la investigación: Article

TY - JOUR

T1 - In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization

AU - Varas-Godoy, Manuel

AU - Lladser, Alvaro

AU - Farfan, Nicole

AU - Villota, Claudio

AU - Villegas, Jaime

AU - Tapia, Julio C.

AU - Burzio, Luis O.

AU - Burzio, Veronica A.

AU - Valenzuela, Pablo D.T.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Lentivirus

KW - Melanoma

KW - Metastasis

KW - Mitochondria

KW - Mouse

KW - NcRNA

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U2 - 10.1111/pcmr.12615

DO - 10.1111/pcmr.12615

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