MiR-124 exerts tumor suppressive functions on the cell proliferation, motility and angiogenesis of bladder cancer by fine-tuning UHRF1

FEBS J. 2015 Nov;282(22):4376-88. doi: 10.1111/febs.13502. Epub 2015 Sep 19.

Abstract

UHRF1, an epigenetic factor, is implicated in various cellular processes of tumorigenesis. However, the modulation of UHRF1 expression in human bladder cancer at post-transcriptional levels remains unclear. Here, we report that miR-124 suppresses expression of UHRF1 to affect the progression of human bladder cancer through competitive binding of the same region of its 3'-UTR. We show that compared with corresponding normal tissues, UHRF1 is upregulated and miR-124 is downregulated in bladder cancer tissues, demonstrating an inverse correlation of miR-124 and UHRF1. Quantitative PCR and western blot assay demonstrated that over-expression of miR-124 resulted in the suppression of UHRF1. Furthermore, luciferase assay revealed that miR-124 could control the fate of target gene UHRF1 mRNA by binding 3'-UTR. The rescue experiment confirmed that miR-124 exerted its biological functions by targeting UHRF1. miR-124 over-expression significantly attenuated cellular proliferation, migration, invasion and vasculogenic mimicry in vitro, and tumor growth in vivo. UHRF1 siRNA showed significant inhibitory effects on bladder cancer cells. Collectively, our study demonstrates that miR-124 can impair the proliferation or metastasis of human bladder cancer cells by down-regulation of UHRF1.

Keywords: UHRF1; bladder cancer; matastasis; miR-124; proliferation.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • DNA Methylation
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic
  • Ubiquitin-Protein Ligases
  • Urinary Bladder Neoplasms / blood supply
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / prevention & control

Substances

  • CCAAT-Enhancer-Binding Proteins
  • MIRN124 microRNA, human
  • MicroRNAs
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases