MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R

  • Authors:
    • Xudong Chen
    • Xufei Zhang
    • Shunjin Sun
    • Meixiao Zhu
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  • Published online on: December 16, 2019     https://doi.org/10.3892/ijmm.2019.4429
  • Pages: 597-606
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Abstract

MicroRNA‑432 (miR‑432) has been studied in multiple tumors, but the expression status, biological functions and the mechanism of action of miR‑432 in glioblastoma multiforme (GBM) are yet to be elucidated. In the present study, miR‑432 expression in GBM was determined and its clinical significance was evaluated among patients with GBM. The effects on the malignancy of GBM in vitro and in vivo were examined in detail and the interactions between miR‑432 and insulin‑like growth factor 1 receptor (IGF‑1R) mRNA were then explored. miR‑432 expression in GBM tissue samples and cell lines was measured by reverse transcription‑quantitative (RT‑q)PCR. GBM cell proliferation, apoptosis, migration and invasion in vitro and tumor growth in vivo were evaluated by a Cell Counting Kit‑8 assay, flow‑cytometric analysis, Transwell migration and invasion assays, and a tumor xenograft experiment, respectively. Bioinformatic analysis followed by a luciferase reporter assay, RT‑qPCR and western blotting was applied to demonstrate that IGF‑1R is a direct target gene of miR‑432 in GBM cells. It was found that miR‑432 is downregulated in GBM tumors and cell lines. miR‑432 under expression obviously correlated with the Karnofsky Performance Status score and shorter overall survival among patients with GBM. Exogenous miR‑432 expression significantly reduced proliferation and induced apoptosis of GBM cells. In addition, miR‑432 overexpression impaired the migratory and invasive abilities of GBM cells in vitro and decreased their tumor growth in vivo. Furthermore, IGF‑1R was validated as a direct target gene of miR‑432 in GBM cells. IGF‑1R knockdown imitated the tumor‑suppressive actions of miR‑432 overexpression in GBM cells. Rescue experiments proved IGF‑1R downregulation to be essential for the effects of miR‑432 on GBM cells. The results of the present study revealed a tumor‑suppressive role of the miR‑432‑IGF‑1R axis in GBM cells and this axis may have implications for GBM therapy.
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February 2020
Volume 45 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Chen, X., Zhang, X., Sun, S., & Zhu, M. (2020). MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R. International Journal of Molecular Medicine, 45, 597-606. https://doi.org/10.3892/ijmm.2019.4429
MLA
Chen, X., Zhang, X., Sun, S., Zhu, M."MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R". International Journal of Molecular Medicine 45.2 (2020): 597-606.
Chicago
Chen, X., Zhang, X., Sun, S., Zhu, M."MicroRNA‑432 inhibits the aggressiveness of glioblastoma multiforme by directly targeting IGF‑1R". International Journal of Molecular Medicine 45, no. 2 (2020): 597-606. https://doi.org/10.3892/ijmm.2019.4429