title: Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy.
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.
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhao
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Yan-Feng
authors.initials: YF
authors.lastname: Song
authors.affiliation: Department of Urology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Niu
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.|Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, China.
authors.forename: Ying-Xia
authors.initials: YX
authors.lastname: Tian
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Xu-Guang
authors.initials: XG
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Jing
authors.affiliation: Department of Anatomy and Histology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
authors.forename: De-Gui
authors.initials: DG
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D003114:Colony-Forming Units Assay; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005455:Fluorescent Antibody Technique; D005720:Gamma Rays; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; C486521:RNF8 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: RNF8; adenovirus; bladder cancer; gene therapy; radiotherapy