MicroRNA-222 promotes tumorigenesis via targeting DKK2 and activating the Wnt/β-catenin signaling pathway

FEBS Lett. 2013 Jun 19;587(12):1742-8. doi: 10.1016/j.febslet.2013.04.002. Epub 2013 Apr 12.

Abstract

MiR-222 in glioma can regulate cell cycle progression and apoptosis. However, the relationship between miR-222 and Wnt/β-catenin signaling pathway in glioma remains unknown. Here, we found that the Dickkopf-2 gene (DKK2) was a direct target of miR-222 by target prediction analysis and dual luciferase reporter assay. RNA interference silencing of DKK2 proved that miR-222 overexpression led to constitutive activation of β-catenin through inhibition of DKK2 expression in glioma cells. Furthermore, miR-222 siRNA significantly inhibited tumorigenesis in vivo. Finally, Western blot analysis showed that miR-222 could regulate the expression of β-catenin and the downstream genes of Wnt/β-catenin signaling pathway. Taken together, our findings reveal a new regulatory mechanism of miR-222 and suggest that miR-222 might be a potential target in glioma therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • DKK2 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN222 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Wnt Proteins
  • beta Catenin