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In vivo knockdown of antisense non‐coding mitochondrial RNA s by a lentiviral‐encoded sh RNA inhibits melanoma tumor growth and lung colonization
Author(s) -
VarasGodoy Manuel,
Lladser Alvaro,
Farfan Nicole,
Villota Claudio,
Villegas Jaime,
Tapia Julio C.,
Burzio Luis O.,
Burzio Veronica A.,
Valenzuela Pablo D. T.
Publication year - 2018
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12615
Subject(s) - gene knockdown , rna , antisense rna , in vivo , long non coding rna , biology , melanoma , cancer research , microbiology and biotechnology , gene , genetics
Summary The family of non‐coding mitochondrial RNA s (ncmt RNA ) is differentially expressed according to proliferative status. Normal proliferating cells express sense (Sncmt RNA ) and antisense ncmt RNA s ( AS ncmt RNA s), whereas tumor cells express Sncmt RNA and downregulate AS ncmt RNA s. Knockdown of AS ncmt RNA s 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 AS ncmt RNA s in melanoma cell lines with a lentiviral‐encoded sh RNA approach. Transduction with lentiviral constructs targeted to the AS ncmt RNA s 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 ncmt RNA s for cancer therapy and validate lentiviral–sh RNA vectors for gene therapy.