Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy

Oncotarget. 2016 Feb 23;7(8):8956-67. doi: 10.18632/oncotarget.6909.

Abstract

The ubiquitin ligase RNF8 promotes the DNA damage response (DDR). We observed that the expression of RNF8 was increased in bladder cancer cells and that this change in RNF8 expression could be reversed by adenovirus-mediated shRNA treatment. Moreover, we found that RNF8 knockdown sensitized bladder cancer cells to radiotherapy, as demonstrated by reduced cell survival. Additionally, the absence of RNF8 induced a high rate of apoptosis and impaired double-strand break repair signaling after radiotherapy. Furthermore, experiments on nude mice showed that combining shRNF8 treatment with radiotherapy suppressed implanted bladder tumor growth and enhanced apoptotic cell death in vivo. Altogether, our results indicated that RNF8 might be a novel target for bladder cancer treatment.

Keywords: RNF8; adenovirus; bladder cancer; gene therapy; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Blotting, Western
  • Colony-Forming Units Assay
  • DNA Damage / genetics*
  • DNA Damage / radiation effects
  • DNA Repair / genetics
  • DNA Repair / radiation effects
  • DNA-Binding Proteins / antagonists & inhibitors*
  • DNA-Binding Proteins / genetics
  • Fluorescent Antibody Technique
  • Gamma Rays
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • RNA, Small Interfering / genetics*
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligases
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / radiotherapy*
  • Xenograft Model Antitumor Assays

Substances

  • DNA-Binding Proteins
  • RNA, Small Interfering
  • RNF8 protein, human
  • Ubiquitin-Protein Ligases