Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells

  • Authors:
    • Liyao Xu
    • Hua Liu
    • Zhangming Yan
    • Zhirong Sun
    • Shiwen Luo
    • Quqin Lu
  • View Affiliations

  • Published online on: April 4, 2017     https://doi.org/10.3892/ijo.2017.3946
  • Pages: 1868-1878
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Abstract

Multiple lines of evidence indicate that aberrant activation of Hedgehog (Hh) signaling plays an important role in tumorigenesis in human glioma. However, the underlying molecular mechanism and crucial downstream targets of glioma-associated oncogene (Gli), a primary transcriptional regulator of Hh signaling, are not fully understood. Here, we report the identification of miR-124 as a novel downstream target of the transcriptional factor Gli2, which is important for proliferation and tumor growth in human glioma cells. Blockade of Hh signaling leads to a remarkable increase in miR-124 expression in glioma cells, whereas overexpression of Gli2 suppresses miR-124 expression by increasing the direct binding of Gli2 to the upstream region of the transcriptional start site for miR-124. Furthermore, we found that miR-124 potentially interacts with the 3'-UTR region of AURKA. Overexpression of miR-124 significantly decreased the expression of AURKA in glioma cells. In contrast, the loss of miR-124 led to the increased expression of AURKA mRNA and protein. In addition, cell proliferation and colony formation ability were significantly decreased following Gli2 knockdown in human glioma cells, while transfection with a miR-124 inhibitor rescued the proliferative ability of cells. These results demonstrate that miR-124 is an important downstream target gene of Hh signaling, and the Gli2/miR-124/AURKA axis is essential for the proliferation and growth of human glioma cells.
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May-2017
Volume 50 Issue 5

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

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Spandidos Publications style
Xu L, Liu H, Yan Z, Sun Z, Luo S and Lu Q: Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells. Int J Oncol 50: 1868-1878, 2017
APA
Xu, L., Liu, H., Yan, Z., Sun, Z., Luo, S., & Lu, Q. (2017). Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells. International Journal of Oncology, 50, 1868-1878. https://doi.org/10.3892/ijo.2017.3946
MLA
Xu, L., Liu, H., Yan, Z., Sun, Z., Luo, S., Lu, Q."Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells". International Journal of Oncology 50.5 (2017): 1868-1878.
Chicago
Xu, L., Liu, H., Yan, Z., Sun, Z., Luo, S., Lu, Q."Inhibition of the Hedgehog signaling pathway suppresses cell proliferation by regulating the Gli2/miR-124/AURKA axis in human glioma cells". International Journal of Oncology 50, no. 5 (2017): 1868-1878. https://doi.org/10.3892/ijo.2017.3946