Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
Biomed Pharmacother. 2018 Aug;104:420-426. doi: 10.1016/j.biopha.2018.05.048. Epub 2018 May 25.
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-κB 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.
越来越多的证据表明 microRNA-216b（miR-216b）在各种癌症的发生和发展中发挥着重要作用。然而，miR-216b 在神经胶质瘤中的功能知之甚少。在本研究中，我们旨在研究 miR-216b 在神经胶质瘤中的表达水平和功能意义。我们发现 miR-216b 在神经胶质瘤标本和细胞系中显著下调。miR-216b 的过表达抑制了神经胶质瘤细胞的生长和迁移，而 miR-216b 的抑制则表现出相反的效果。生物信息学分析预测星形细胞上调基因-1（AEG-1）是 miR-216b 的潜在靶基因。双荧光素酶报告基因实验表明，miR-216b 可以直接靶向 AEG-1 的 3'-非翻译区。RT-qPCR 和 Western blot 分析表明，miR-216 在神经胶质瘤细胞中负调控 AEG-1 的表达。相关性分析显示 miR-216b 与临床神经胶质瘤标本中的 AEG-1 呈负相关。miR-216b 还调节神经胶质瘤细胞中核因子-κB 和 Wnt 信号的激活。此外，AEG-1 表达的恢复部分逆转了 miR-216b 过表达对神经胶质瘤细胞生长和迁移的抑制作用。总之，这些结果揭示了 miR-216b 在神经胶质瘤发生中的肿瘤抑制作用，并确定 AEG-1 是 miR-216b 作用的靶基因。我们的研究表明，miR-216b 可作为神经胶质瘤新疗法的潜在靶点。
