miR-590-3p suppresses cancer cell migration, invasion and epithelial-mesenchymal transition in glioblastoma multiforme by targeting ZEB1 and ZEB2
miR-590-3p suppresses cancer cell migration, invasion and epithelial-mesenchymal transition in glioblastoma multiforme by targeting ZEB1 and ZEB2
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DOI：
10.1016/j.bbrc.2015.11.025
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发表时间：
2015-12-25
影响因子：
3.1
通讯作者：
Wang, Jianjiao
中科院分区：
文献类型：
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作者：
Pang, Hengyuan;Zheng, Yongri;Wang, Jianjiao
多形性胶质母细胞瘤（GBM）的侵袭和迁移是一个多步骤的过程，是导致该疾病侵袭脑中周围组织的重要表型。本研究的目的是确定miR-590- 3 p在GBM细胞的上皮间质转化（EMT）和转移中的调节作用。通过定量RT-PCR评估15例GBM标本及其邻近组织和5个GBM细胞系中miR-590- 3 p的表达水平。我们发现miR-590- 3 p在检测到的GBM组织样品和所有GBM细胞系中下调。此外，miR-590- 3 p的异位表达抑制了U87 MG和A172细胞中的EMT、迁移和侵袭，而miR-590- 3 p-in促进了U87 MG和A172细胞中的EMT、迁移和侵袭。生物信息学结合荧光素酶和蛋白质印迹分析还显示，miR-590- 3 p抑制了ZEB 1和ZEB 2的表达，这是肿瘤转移的主要调节因子。我们的研究首次表明miR-590- 3 p通过靶向ZEB 1和ZEB 2抑制GBM EMT和转移，可能成为转移性GBM的治疗靶点。(C)2015 Elsevier Inc. All rights reserved.
Invasion and migration of glioblastoma multiforme (GBM) is a multistep process and an important phenotype that causes this disease to invade surrounding tissues in the brain. The purpose of this study was to determine the role of miR-590-3p in regulation of epithelial mesenchymal transition (EMT) and metastasis of GBM cells. Expression levels of miR-590-3p in 15 GBM specimens with adjacent tissues and five GBM cell lines were assessed by quantitative RT-PCR. We found that miR-590-3p was down-regulated in detected GBM tissue samples and all of the GBM cell lines. In addition, Ectopic expression of miR-590-3p suppressed and miR-590-3p-in promoted EMT, migration, and invasion in U87MG and A172 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-590-3p inhibited expression of ZEB1 and ZEB2, which are master regulators of tumor metastasis. Our study first indicates that miR-590-3p functions as a suppressor of GBM EMT and metastasis by targeting ZEB1 and ZEB2, and it may be a therapeutic target for metastatic GBM. (C) 2015 Elsevier Inc. All rights reserved.