期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 52, 期 2, 页码 485-495出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2017.4217
关键词
glioblastoma; miRNA; ZEB1; epithelial-mesenchymal transition; migration; invasion
类别
资金
- National Natural Science Foundation of China [81703011, 81272774, 81572497]
- Science Foundation of Guangzhou Women and Children's Medical Center [5001-3001023, 5001-2150010]
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.
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