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 original | English |
|---|---|
| Páginas (desde-hasta) | 64-72 |
| Número de páginas | 9 |
| Publicación | Pigment Cell and Melanoma Research |
| Volumen | 31 |
| N.º | 1 |
| DOI | |
| Estado | Accepted/In press - 1 ene 2017 |
Huella dactilar
ASJC Scopus subject areas
- Oncology
- Biochemistry, Genetics and Molecular Biology(all)
- Dermatology
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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
UR - http://www.scopus.com/inward/record.url?scp=85031738702&partnerID=8YFLogxK
U2 - 10.1111/pcmr.12615
DO - 10.1111/pcmr.12615
M3 - Article
AN - SCOPUS:85031738702
VL - 31
SP - 64
EP - 72
JO - Pigment Cell and Melanoma Research
JF - Pigment Cell and Melanoma Research
SN - 1755-1471
IS - 1
ER -