Abstract 4181: Oncogenic microRNA-183 induces cell growth and motility through down-regulation of Dkk-3 and SMAD4 in bladder cancer.

Abstract

Abstract Introduction and Objective : The purpose of this study was to carry out functional analysis of oncogenic microRNA-183 and identify their specific target genes in bladder cancer. Methods : Expression levels of miR-183 in bladder normal/cancer tissues and bladder cancer cell lines were confirmed using real-time PCR. To examine the function of miR-183, cell growth, and migration were performed using UM-UC-3 cells because the miR-183 expression level was highest among bladder cancer cell lines. To search for target genes of miR-183, we used a target scan algorithm and performed Dkk-3 and SMAD4 3’UTR luciferase assays. To analyze whether Dkk-3 and SMAD4 affect cell growth and motility, Dkk-3 and SMAD4 expressing plasmids were transfected into UM-UC-3 cells and cell growth and motility were performed. Results: Expression of miR-183 in cancer bladder tissues was significantly up-regulated compared to normal bladder tissues. MiR-183 expression was significantly higher in the pT3+4 tissues than in pT1+2 tissues. Higher miR-183 expression was significantly associated with shorter survival. MiR-183 increased cell growth and migration abilities in UM-UC-3 cells. MiR-183 decreased 3’UTR luciferase activity of Dkk-3 and SMAD4. Cell growth and motility was significantly decreased in Dkk-3 and SMAD4 transfected cells compared with control cells. Conclusions : MiR-183 is a oncogenic microRNA in bladder cancer through down-regulation of Dkk-3 and SMAD4. Citation Format: Koji Ueno, Hiroshi Hirata, Varahram Shahryari, Yuichiro Tanaka, Z. Laura Tabatabai, Yuji Hinoda, Rajvir Dahiya. Oncogenic microRNA-183 induces cell growth and motility through down-regulation of Dkk-3 and SMAD4 in bladder cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4181. doi:10.1158/1538-7445.AM2013-4181