Tumor suppressor microRNA-493 decreases cell motility and migration ability in human bladder cancer cells by downregulating RhoC and FZD4

Mol Cancer Ther. 2012 Jan;11(1):244-53. doi: 10.1158/1535-7163.MCT-11-0592. Epub 2011 Nov 4.

Abstract

The purpose of this study was to identify new tumor suppressor microRNAs (miRNA; miR) in bladder cancer, conduct functional analysis of their suppressive role, and identify their specific target genes. To explore tumor suppressor miRs in bladder cancer, miR microarray was conducted using SV-HUC-1, T24, J82, and TCCSUP cells. Expression of miR-493 in bladder cancer (T24, J82, and TCCSUP) cells was downregulated compared with normal SV-HUC-1 cells. Also, the expression of miR-493 was significantly lower in bladder cancer tissues than in their corresponding noncancerous tissues. Transfection of miR-493 into T24 or J82 cells decreased their cell growth and migration abilities. On the basis of this result, to identify potential miR-493 target genes, we used target scan algorithms to identify target oncogenes related to invasion and migration. miR-493 decreased 3'-untranslated region luciferase activity and protein expression of FZD4 and RhoC. miR-493 also decreased binding of RhoC and Rock-1. miR-493 is a new tumor suppressor miRNA in bladder cancer and inhibits cell motility through downregulation of RhoC and FZD4.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Survival
  • Down-Regulation
  • Frizzled Receptors / genetics
  • Frizzled Receptors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology
  • RNA Interference
  • RNA, Small Interfering
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*
  • rhoC GTP-Binding Protein

Substances

  • 3' Untranslated Regions
  • FZD4 protein, human
  • Frizzled Receptors
  • MIRN493 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoC GTP-Binding Protein