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Article

IDH1 mutation diminishes aggressive phenotype in glioma stem cells

  • Authors:
    • Qi Yao
    • Gang Cai
    • Qi Yu
    • Jianhong Shen
    • Zhikai Gu
    • Jian Chen
    • Wei Shi
    • Jinlong Shi
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Neurosurgery, The First People's Hospital of Nantong, Nantong, Jiangsu 226001, P.R. China
  • Pages: 270-278
    |
    Published online on: November 3, 2017
       https://doi.org/10.3892/ijo.2017.4186
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Abstract

The R132H mutation in isocitrate dehydrogenase 1 (IDH1-R132H) is associated with better prognosis in glioma patients. Glioma stem cells (GSCs) in glioma are believed to be responsible for glioma growth and maintenance. However, the relation between the R132H mutation and GSCs is not fully understood. In the present study, GSC markers were detected in patients with IDH1-R132H or wild-type IDH1 (IDH1-wt) by tissue microarray immunohistochemistry (TMA-IHC). The relationship between the expression patterns of GSC markers and the clinicopathological characteristics in glioma were analyzed. To confirm this mutation's role in GSCs, the IDH1-R132H in GSCs isolated from glioblastoma patients with IDH1 mutations was overexpressed by using lentiviral constructs in vitro, and then the proliferation, differentiation, apoptosis, migration and invasion of the transfected GSCs were explored. At the molecular level, we detected Wnt/β-catenin signaling expression to verify its role in regulating the cellular properties of GSCs. The results showed that the positive rate of GSCs in patients with IDH1-R132H was significantly less than that in patients with IDH1-wt. The positive rate of GSCs was correlated with IDH1 mutation, TNM stage and poor overall survive. After transfection in vitro, IDH1-R132H overexpression led to reduced GSCs proliferation, migration and invasion, inducing apoptosis and improving GSC differentiation, accompanied by a significant reduction in activity of β-catenin. Several mediators, effectors and targets of the Wnt/β-catenin signaling were downregulated. The data demonstrate that IDH1 mutation reduces the malignant progression of glioma by causing a less aggressive phenotype of GSCs which are involved in the Wnt/β‑catenin signaling.
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Copy and paste a formatted citation
Spandidos Publications style
Yao Q, Cai G, Yu Q, Shen J, Gu Z, Chen J, Shi W and Shi J: IDH1 mutation diminishes aggressive phenotype in glioma stem cells. Int J Oncol 52: 270-278, 2018.
APA
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J. ... Shi, J. (2018). IDH1 mutation diminishes aggressive phenotype in glioma stem cells. International Journal of Oncology, 52, 270-278. https://doi.org/10.3892/ijo.2017.4186
MLA
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J., Shi, W., Shi, J."IDH1 mutation diminishes aggressive phenotype in glioma stem cells". International Journal of Oncology 52.1 (2018): 270-278.
Chicago
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J., Shi, W., Shi, J."IDH1 mutation diminishes aggressive phenotype in glioma stem cells". International Journal of Oncology 52, no. 1 (2018): 270-278. https://doi.org/10.3892/ijo.2017.4186
Copy and paste a formatted citation
x
Spandidos Publications style
Yao Q, Cai G, Yu Q, Shen J, Gu Z, Chen J, Shi W and Shi J: IDH1 mutation diminishes aggressive phenotype in glioma stem cells. Int J Oncol 52: 270-278, 2018.
APA
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J. ... Shi, J. (2018). IDH1 mutation diminishes aggressive phenotype in glioma stem cells. International Journal of Oncology, 52, 270-278. https://doi.org/10.3892/ijo.2017.4186
MLA
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J., Shi, W., Shi, J."IDH1 mutation diminishes aggressive phenotype in glioma stem cells". International Journal of Oncology 52.1 (2018): 270-278.
Chicago
Yao, Q., Cai, G., Yu, Q., Shen, J., Gu, Z., Chen, J., Shi, W., Shi, J."IDH1 mutation diminishes aggressive phenotype in glioma stem cells". International Journal of Oncology 52, no. 1 (2018): 270-278. https://doi.org/10.3892/ijo.2017.4186
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