Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors
Author
dc.contributor.author
Borgna Christie, Vincenzo
Author
dc.contributor.author
Lobos González, Lorena
Author
dc.contributor.author
Guevara, Francisca
Author
dc.contributor.author
Landerer, Eduardo
Author
dc.contributor.author
Bendek, Maximiliano
Author
dc.contributor.author
Ávila, Rodolfo
Author
dc.contributor.author
Silva, Verónica
Author
dc.contributor.author
Villota, Claudio
Author
dc.contributor.author
Araya, Mariela
Author
dc.contributor.author
Rivas, Alexis
Author
dc.contributor.author
López, Constanza
Author
dc.contributor.author
Socias, Teresa
Author
dc.contributor.author
Castillo, Jorge
Author
dc.contributor.author
Alarcón Navarrete, Luis
Author
dc.contributor.author
Burzio, Luis O.
Author
dc.contributor.author
Burzio, Verónica A.
Author
dc.contributor.author
Villegas, Jaime
Admission date
dc.date.accessioned
2020-05-11T22:32:18Z
Available date
dc.date.available
2020-05-11T22:32:18Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Journal of Cancer 2020, Vol. 11
es_ES
Identifier
dc.identifier.other
10.7150/jca.38880
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/174666
Abstract
dc.description.abstract
Knockdown 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.
es_ES
Patrocinador
dc.description.sponsorship
Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) Fondecyt-1140345 Fondef-D04I1338 Basal AFB 170004
Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors