Oncogenic miRNA-182-5p targets Smad4 and RECK in human bladder cancer

PLoS One. 2012;7(11):e51056. doi: 10.1371/journal.pone.0051056. Epub 2012 Nov 30.

Abstract

Onco-miR-182-5p has been reported to be over-expressed in bladder cancer (BC) tissues however a detailed functional analysis of miR-182-5p has not been carried out in BC. Therefore the purpose of this study was to: 1. conduct a functional analysis of miR-182-5p in bladder cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in BC. Initially we found that miR-182-5p expression was significantly higher in bladder cancer compared to normal tissues and high miR-182-5p expression was associated with shorter overall survival in BC patients. To study the functional significance of miR-182-5p, we over-expressed miR-182-5p with miR-182-5p precursor and observed that cell proliferation, migration and invasion abilities were increased in BC cells. However cell apoptosis was inhibited by miR-182-5p. We also identified Smad4 and RECK as potential target genes of miR-182-5p using several algorithms. 3'UTR luciferase activity of these target genes was significantly decreased and protein expression of these target genes was significantly up-regulated in miR-182-5p inhibitor transfected bladder cancer cells. MiR-182-5p also increased nuclear beta-catenin expression and while Smad4 repressed nuclear beta-catenin expression. In conclusion, our data suggests that miR-182-5p plays an important role as an oncogene by knocking down RECK and Smad4, resulting in activation of the Wnt-beta-catenin signaling pathway in bladder cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Nucleus / metabolism
  • Cell Survival / genetics
  • GPI-Linked Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Oncogenes / genetics*
  • Smad4 Protein / metabolism*
  • Survival Analysis
  • Transfection
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • beta Catenin / metabolism

Substances

  • 3' Untranslated Regions
  • GPI-Linked Proteins
  • MicroRNAs
  • Mirn182 microRNA, human
  • RECK protein, human
  • SMAD4 protein, human
  • Smad4 Protein
  • beta Catenin
  • Luciferases