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

Borgna, Vincenzo; Lobos-Gonzalez, Lorena; Guevara, Francisca; Landerer, Eduardo; Bendek, Maximiliano; Avila, Rodolfo; Silva, Veronica; Villota, Claudio; Araya, Mariela; Rivas, Alexis; Lopez, Constanza; Socias, Teresa; Castillo Jorge; Alarcon, Luis; Burzio, Luis O.; et. al.

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.

Más información

Título según WOS: Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors
Título según SCOPUS: Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors
Título de la Revista: JOURNAL OF CANCER
Volumen: 11
Número: 7
Editorial: IVYSPRING INT PUBL
Fecha de publicación: 2020
Página de inicio: 1780
Página final: 1791
Idioma: English
DOI:

10.7150/jca.38880

Notas: ISI, SCOPUS