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

  • Authors:
    • Wei Chen
    • Kuan-Kei Kong
    • Xin-Ke Xu
    • Cheng Chen
    • Hui Li
    • Fang-Yu Wang
    • Xiao-Fang Peng
    • Zhan Zhang
    • Ping Li
    • Jun-Liang Li
    • Fang-Cheng Li
  • View Affiliations

  • Published online on: December 6, 2017     https://doi.org/10.3892/ijo.2017.4217
  • Pages: 485-495
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Abstract

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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February-2018
Volume 52 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chen W, Kong K, Xu X, Chen C, Li H, Wang F, Peng X, Zhang Z, Li P, Li J, Li J, et al: 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. Int J Oncol 52: 485-495, 2018
APA
Chen, W., Kong, K., Xu, X., Chen, C., Li, H., Wang, F. ... Li, F. (2018). 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. International Journal of Oncology, 52, 485-495. https://doi.org/10.3892/ijo.2017.4217
MLA
Chen, W., Kong, K., Xu, X., Chen, C., Li, H., Wang, F., Peng, X., Zhang, Z., Li, P., Li, J., Li, F."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". International Journal of Oncology 52.2 (2018): 485-495.
Chicago
Chen, W., Kong, K., Xu, X., Chen, C., Li, H., Wang, F., Peng, X., Zhang, Z., Li, P., Li, J., Li, F."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". International Journal of Oncology 52, no. 2 (2018): 485-495. https://doi.org/10.3892/ijo.2017.4217