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

• DKK2 was identified as a direct target of miR-222.
• MiR-222 siRNA significantly inhibits tumorigenesis in vivo.
• MiR-222 overexpression promotes tumorigenesis via targeting DKK2.
• Mir-222 regulates β-catenin and the downstream genes of Wnt/β-catenin signaling pathway.

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.