Downregulation of miR-205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway
Downregulation of miR-205 is associated with glioblastoma cell migration, invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the Akt/mTOR signaling pathway
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通过 Akt/mTOR 信号通路靶向 ZEB1，miR-205 的下调与胶质母细胞瘤细胞迁移、侵袭和上皮间质转化相关
DOI：
10.3892/ijo.2017.4217
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发表时间：
2018-02-01
影响因子：
5.2
通讯作者：
Li, Fang-Cheng
中科院分区：
文献类型：
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作者：
Chen, Wei;Kong, Kuan-Kei;Li, Fang-Cheng
胶质母细胞瘤（GBM）是最常见的恶性脑肿瘤类型。尽管最近在手术技术、化疗和放射治疗方面取得了进展，但GBM患者通常面临可怕的预后。MicroRNA已被证明可调节各种癌症的侵袭性，并已成为管理GBM的可能治疗剂。miR-205在胶质瘤中失调，并作为预后指标。然而，miR-205在GBM发展中的作用尚未阐明。为了更好地了解GBM的发病机制，我们研究了miR-205在GBM细胞中的生物学意义和分子机制。锌指E盒结合同源异型盒1（ZEB 1）已被证明调节上皮-间质转化（EMT），EMT与GBM恶性肿瘤密切相关。在本研究中，我们发现miR-205在GBM组织和细胞系中表达减少，ZEB 1表达与miR-205表达呈负相关。我们还发现ZEB 1是miR-205的下游靶点，当miR-205与ZEB 1相互作用时，Akt/mTOR信号通路被激活。miR-205在GBM细胞中的活性增加显著抑制迁移和侵袭，并防止EMT。此外，ZEB 1的过表达部分消除了miR-205的这些抑制作用。我们发现，miR-205负调控GBM中ZEB 1的表达，抑制细胞迁移和侵袭，并防止EMT，至少部分通过抑制Akt/mTOR信号通路的激活。我们的结果表明miR-205可能是治疗GBM的有效治疗剂。
Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of recent advancements in surgical techniques, chemotherapy, and radiation therapy, patients with GBM often face a dire prognosis. MicroRNAs have been shown to modulate the aggressiveness of various cancers, and have emerged as possible therapeutic agents for the management of GBM. miR-205 is dysregulated in glioma and act as a prognostic indicator. However, the role of miR-205 in the development of GBM has not been elucidated. To better understand the pathogenesis of GBM, we examine the biological significance and molecular mechanisms of miR-205 in GBM cells. Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to regulate the epithelial-mesenchymal transition (EMT), which is strongly associated with GBM malignancy. In the present study, we show miR-205 expression is reduced in GBM tissues and cell lines, and ZEB1 expression is inversely correlated with miR-205 expression. We also show ZEB1 is a downstream target of miR-205 and the Akt/mTOR signaling pathway is activated when miR-205 interacts with ZEB1. Increased activity of miR-205 in GBM cells significantly inhibits migration and invasion, and prevents EMT. Furthermore, overexpression of ZEB1 partially abolishes these inhibitory effects of miR-205. We show that miR-205 negatively regulates the expression of ZEB1 in GBM, inhibits cell migration and invasion, and prevents EMT, at least in part through the inhibition of the activation of the Akt/mTOR signaling pathway. Our results indicate miR-205 may be an efficacious therapeutic agent in the treatment of GBM.