Department of Pediatric Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, PR China.
FEBS Lett. 2013 Jun 19;587(12):1742-8. doi: 10.1016/j.febslet.2013.04.002. Epub 2013 Apr 12.
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.
miR-222 在神经胶质瘤中可以调节细胞周期进程和细胞凋亡。然而，miR-222 与神经胶质瘤中的 Wnt/β-连环蛋白信号通路之间的关系尚不清楚。在这里，我们通过靶标预测分析和双荧光素酶报告基因实验发现 Dickkopf-2 基因（DKK2）是 miR-222 的直接靶标。DKK2 的 RNA 干扰沉默证明，miR-222 通过抑制神经胶质瘤细胞中 DKK2 的表达，导致 β-连环蛋白的组成性激活。此外，miR-222 siRNA 显著抑制体内肿瘤发生。最后，Western blot 分析表明，miR-222 可以调节 Wnt/β-连环蛋白信号通路的 β-连环蛋白和下游基因的表达。总之，我们的研究结果揭示了 miR-222 的一个新的调控机制，并表明 miR-222 可能是神经胶质瘤治疗的一个潜在靶点。
