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

Vincenzo Borgna, Lorena Lobos-González, Francisca Guevara, Eduardo Landerer, Maximiliano Bendek, Rodolfo Ávila, Verónica Silva, Claudio Villota, Mariela Araya, Alexis Rivas, Constanza López, Teresa Socias, Jorge Castillo, Luis Alarcón, Luis O. Burzio, Verónica A. Burzio, Jaime Villegas

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1780-1791
Number of pages12
JournalJournal of Cancer
Volume11
Issue number7
DOIs
Publication statusPublished - 1 Jan 2020

Keywords

  • Antisense therapy
  • Apoptosis
  • Bladder cancer
  • Noncoding RNA

ASJC Scopus subject areas

  • Oncology

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