miR-637 Prevents Glioblastoma Progression by Interrupting ZEB2/WNT/β-catenin Cascades.

Glioblastomas (GBMs) are the most frequent primary malignancies in the central nervous system. Aberrant activation of WNT/β-catenin signaling pathways is critical for GBM malignancy. However, the regulation of WNT/β-catenin signaling cascades remains unclear. Presently, we observed the increased expression of ZEB2 and the decreased expression of miR-637 in GBM. The expression of miR-637 was negatively correlated with ZEB2 expression. miR-637 overexpression overcame the ZEB2-enhanced cell proliferation and G1/S phase transition. Besides, miR-637 suppressed the canonical WNT/β-catenin pathways by targeting WNT7A directly. Gain- and loss-of-function experiments with U251 mice demonstrated that miR-637 inhibited cell proliferation and arrested the G1/S phase transition, leading to tumor growth suppression. The collective findings suggest that ZEB2 and WNT/β-catenin cascades merge at miR-637, and the ectopic expression of miR-637 disturbs ZEB2/WNT/β-catenin-mediated GBM growth. The findings provide new clues for improving β-catenin-targeted therapy against GBM.