MicroRNA-206 attenuates glioma cell proliferation, migration, and invasion by blocking the WNT/β-catenin pathway via direct targeting of Frizzled 7 mRNA

摘要

Glioma is one of the most prevalent primary malignant brain tumours among adults, and accumulating evidence has shown that dysregulation of microRNAs (miRNAs) is associated with various types of cancers, including glioma. It is necessary to gain a better understanding of the roles and mechanisms of action of miRNAs in WNT-driven glioblastoma multiforme (GBM). Here, we report that miR-206 inhibits the WNT/β-catenin pathway by directly targeting Frizzled 7 ( FZD7 ) mRNA and functions as a tumour suppressor in glioma. The expression of miR-206 in human glioma samples and glioma cells was assessed by reverse-transcription quantitative PCR, fluorescence in situ hybridisation, and histological analysis. Cell Counting Kit-8, colony formation, 5-ethynyl-2’-deoxyuridine incorporation, flow-cytometric, wound healing, Transwell invasion, and three-dimensional migration assays were performed to examine glioma cell proliferation, migration, and invasion in vitro . The effects of miR-206 in vivo were investigated in a xenograft nude-mouse model. MiR-206 expression was significantly lower in glioma specimens than in normal control samples. FZD7 was confirmed as a direct target gene of miR-206. GBM cell proliferation, migration, and invasion were blocked after restoration of miR-206 expression. Moreover, intracranial glioma models revealed an inhibitory effect of miR-206 on intracranial glioma tumour growth. Our results suggest that miR-206 plays a key role in the blockade of the WNT/β-catenin signalling pathway by down-regulating FZD7 and may be a promising therapeutic agent against malignant glioma and other WNT-driven tumours.