Down-regulation of microRNA-224 -inhibites growth and epithelial-to-mesenchymal transition phenotype -via modulating SUFU expression in bladder cancer cells

Int J Biol Macromol. 2018 Jan;106:234-240. doi: 10.1016/j.ijbiomac.2017.07.184. Epub 2017 Aug 2.

Abstract

Aberrant expression of miR-224 is usually found in cancer studies; however, the role of miR-224 has seldom been reported in bladder cancer (BC). We explored miR-224's function and the underlying mechanism in BC. It was found that miR-224 expression was significantly up-regulated in BC tissues and cell lines. Knockdown of miR-224 decreased BC cell growth and invasion both in vitro and in vivo. We identified the SUFU protein as a downstream target of miR-224 by using luciferase and western blot assays. We proposed that miR-224 promoted BC cell growth and invasion via sustaining the activity of Hedgehog pathway, which was negatively regulated by SUFU. Taken together, our study demonstrated that miR-224 may function as an onco-miR in BC and suggested that miR-224 may be a potential therapeutic target for BC patients.

Keywords: Bladder cancer; Sufu; miR-224.

MeSH terms

  • Aged
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Survival Analysis
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology

Substances

  • Antagomirs
  • Hedgehog Proteins
  • MIRN224 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • SUFU protein, human