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

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. © 2012 Wiley Periodicals, Inc.