Downregulation of microRNA-216b contributes to glioma cell growth and migration by promoting AEG-1-mediated signaling

作者:Li, Qi; Wang, Maode*; Wang, Ning; Wang, Jia; Qi, Lei; Mao, Ping
来源:Biomedicine & Pharmacotherapy, 2018, 104: 420-426.
DOI:10.1016/j.biopha.2018.05.048

摘要

Accumulating evidence indicates microRNA-216b (miR-216b) plays an important role in the development and progression of various cancers. However, little is known about the function of miR-216b in gliomas. In this study, we aimed to investigate the expression level and functional significance of miR-216b in gliomas. We found that miR-216b was significantly downregulated in glioma specimens and cell lines. Overexpression of miR-216b suppressed the growth and migration of glioma cells, while miR-216b inhibition showed the opposite effects. Astrocyte elevated gene-1 (AEG-1) was predicted as a potential target gene of miR-216b by bioinformatics analysis. A dual-luciferase reporter assay showed that miR-216b could directly target the 3'-untranslated region of AEG-1. RT-qPCR and western blot analysis showed that miR-216 negatively regulated AEG-1 expression in glioma cells. Correlation analysis revealed an inverse correlation between miR-216b and AEG-1 in clinical glioma specimens. miR-216b also regulated the activation of nuclear factor-kappa B and Wnt signaling in glioma cells. Moreover, restoration of AEG-1 expression partially reversed the inhibitory effect of miR-216b overexpression on glioma cell growth and migration. Overall, these results revealed a tumor suppressive role of miR-216b in glioma tumorigenesis, and identified AEG-1 as a target gene of miR-216b action. Our study suggests that miR-216b can be potentially targeted for the development of novel therapies for gliomas.