Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors.

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dc.contributor.authorBorgna, Vincenzo
dc.contributor.authorLobos-González, Lorena
dc.contributor.authorGuevara, Francisca
dc.contributor.authorLanderer, Eduardo
dc.contributor.authorBendek, Maximiliano
dc.contributor.authorÁvila, Rodolfo
dc.contributor.authorSilva, Verónica
dc.contributor.authorVillota, Claudio
dc.contributor.authorAraya, Mariela
dc.contributor.authorRivas, Alexis
dc.contributor.authorLópez, Constanza
dc.contributor.authorSocías, Teresa
dc.contributor.authorCastillo, Jorge
dc.contributor.authorAlarcón, Luis
dc.contributor.authorBurzio, Luis
dc.contributor.authorBurzio, Verónica
dc.contributor.authorVillegas, Jaime
dc.date.accessioned2020-03-27T15:13:32Z
dc.date.available2020-03-27T15:13:32Z
dc.date.issued2020
dc.descriptionCentro de Medicina Regenerativa (ICIM)
dc.description.abstractKnockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, supporting a selective therapy against different types of cancer. In this work, we evaluated the effects of knockdown of ASncmtRNAs on bladder cancer (BCa). We transfected the BCa cell lines UMUC-3, RT4 and T24 with the specific antisense oligonucleotide Andes-1537S, targeted to the human ASncmtRNAs. Knockdown induced a strong inhibition of cell proliferation and increase in cell death in all three cell lines. As observed in UMUC-3 cells, the treatment triggered apoptosis, evidenced by loss of mitochondrial membrane potential and Annexin V staining, along with activation of procaspase-3 and downregulation of the anti-apoptotic factors survivin and Bcl-xL. Treatment also inhibited cell invasion and spheroid formation together with inhibition of N-cadherin and MMP 11. In vivo treatment of subcutaneous xenograft UMUC-3 tumors in NOD/SCID mice with Andes-1537S induced inhibition of tumor growth as compared to saline control. Similarly, treatment of a high-grade bladder cancer PDX with Andes-1537S resulted in a strong inhibition of tumor growth. Our results suggest that ASncmtRNAs could be potent targets for bladder cancer as adjuvant therapy.
dc.identifier.citationJ Cancer. 2020 Jan 17;11(7):1780-1791. doi: 10.7150/jca.38880
dc.identifier.urihttp://hdl.handle.net/11447/3185
dc.identifier.urihttps://dx.doi.org/10.7150/jca.38880
dc.language.isoen
dc.publisherIvyspring International Publisher
dc.subjectAntisense therapy
dc.subjectApoptosis
dc.subjectBladder cancer
dc.subjectNoncoding RNA
dc.titleTargeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors.
dc.typeArticle

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