Inducing cell proliferation inhibition and apoptosis via silencing Dicer, Drosha, and Exportin 5 in urothelial carcinoma of the bladder

J Surg Oncol. 2013 Feb;107(2):201-5. doi: 10.1002/jso.23214. Epub 2012 Jul 5.

Abstract

Background and objectives: MicroRNAs (miRNAs) are aberrantly expressed in cancers. Dicer, Drosha, and Exportin 5 are essential for miRNA processing. In this study, the expression patterns of Dicer, Drosha, and Exportin 5 and the cell proliferation inhibition and apoptosis induced by silencing these genes in urothelial carcinoma of the bladder were determined.

Methods: The expression levels of Dicer, Drosha, and Exportin 5 were determined using Real-Time qPCR in 40 patients with urothelial carcinoma of the bladder. Bladder urothelial carcinoma T24 and 5637 cells were transfected with Dicer, Drosha, or Exportin 5 siRNA or negative control siRNA. Cell proliferation was determined using MTT assay. Apoptosis was evaluated using ELISA assay.

Results: All the three genes were up-regulated in bladder urothelial carcinoma compared to matched normal urothelium. Dicer, Drosha, and Exportin 5 expression levels were higher in high grade carcinomas than that in low grade carcinomas. Invasive carcinomas had higher expression levels than non-invasive carcinomas. Silencing Dicer, Drosha, or Exportin 5 induced cell proliferation inhibition and apoptosis in bladder urothelial carcinoma T24 and 5637 cells.

Conclusions: Dicer, Drosha, and Exportin 5 are promising biomarkers and therapeutic targets for urothelial carcinoma of the bladder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Genetic Markers
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • RNA Interference*
  • Real-Time Polymerase Chain Reaction
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*
  • Transfection
  • Up-Regulation
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / metabolism
  • Urothelium / pathology

Substances

  • Biomarkers, Tumor
  • Genetic Markers
  • Karyopherins
  • XPO5 protein, human
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases