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MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1

  • Authors:
    • Yanwei Liu
    • Wei Yan
    • Wei Zhang
    • Lingchao Chen
    • Gan You
    • Zhaoshi Bao
    • Yongzhi Wang
    • Hongjun Wang
    • Chunsheng Kang
    • Tao Jiang

  • View Affiliations

  • Published online on: July 5, 2012     https://doi.org/10.3892/or.2012.1902
  • Pages: 1013-1021
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Abstract

The invasive behavior of glioblastoma multiforme (GBM) cells is one of the most important reasons for the poor prognosis of this cancer. For invasion, tumor cells must acquire an ability to digest the extracellular matrix and infiltrate the normal tissue bordering the tumor. Preventing this by altering effector molecules can significantly improve a patient's prognosis. Accumulating evidence suggests that miRNAs are involved in multiple biological functions, including cell invasion, by altering the expression of multiple target genes. The expression levels of miR-218 correlate with the invasive potential of GBM cells. In this study, we found that miR-218 expression was low in glioma tissues, especially in GBM. The data showed an inverse correlation in 60 GBM tissues between the levels of miR-218 and MMP mRNAs (MMP-2, -7 and -9). Additionally, ectopic expression of miR-218 suppressed the invasion of GBM cells whereas inhibition of miR-218 expression enhanced the invasive ability. Numerous members of the MMP family are downstream effectors of the Wnt/LEF1 pathway. Target prediction databases and luciferase data showed that LEF1 is a new direct target of miR-218. Importantly, western blot assays demonstrated that miR-218 can reduce protein levels of LEF1 and MMP-9. We, therefore, hypothesize that miR-218 directly targets LEF1, resulting in reduced synthesis of MMP-9. Results suggest that miR-218 is involved in the invasive behavior of GBM cells and by targeting LEF1 and blocking the invasive axis, miR-218-LEF1-MMPs, it may be useful for developing potential clinical strategies.
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September 2012
Volume 28 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Journal Metrics
  • Impact Factor: 3.8
  • Ranked Oncology
    (total number of cites)
  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Liu Y, Yan W, Zhang W, Chen L, You G, Bao Z, Wang Y, Wang H, Kang C, Jiang T, Jiang T, et al: MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1. Oncol Rep 28: 1013-1021, 2012.
APA
Liu, Y., Yan, W., Zhang, W., Chen, L., You, G., Bao, Z. ... Jiang, T. (2012). MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1. Oncology Reports, 28, 1013-1021. https://doi.org/10.3892/or.2012.1902
MLA
Liu, Y., Yan, W., Zhang, W., Chen, L., You, G., Bao, Z., Wang, Y., Wang, H., Kang, C., Jiang, T."MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1". Oncology Reports 28.3 (2012): 1013-1021.
Chicago
Liu, Y., Yan, W., Zhang, W., Chen, L., You, G., Bao, Z., Wang, Y., Wang, H., Kang, C., Jiang, T."MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1". Oncology Reports 28, no. 3 (2012): 1013-1021. https://doi.org/10.3892/or.2012.1902