miR-637 prevents glioblastoma progression by interrupting ZEB2/WNT/β-catenin cascades

Abstract 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 decreased expression of miR-637 in GBM. The expression of miR-637 was negatively correlated with expression of ZEB2. miR-637 overexpression overcame the ZEB2-enhanced cell proliferation and G1/S phase transition. In addition, miR-637 suppressed canonical WNT/β-catenin pathways by targeting WNT7A directly. Gain- and loss-of-function experiments in 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 should inform improved β-catenin-targeted therapy against GBM.