DNA methylation-mediated caspase-8 downregulation is associated with anti-apoptotic activity and human malignant glioma grade

  • Authors:
    • Yueqiu Teng
    • Yu‑Cui Dong
    • Zhaoyu Liu
    • Yan Zou
    • Hui Xie
    • Yu Zhao
    • Jun Su
    • Fenglin Cao
    • Hua Jin
    • Huan Ren
  • View Affiliations

  • Published online on: February 7, 2017     https://doi.org/10.3892/ijmm.2017.2881
  • Pages: 725-733
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Abstract

The methylation-mediated silencing of tumor suppressors, including key apoptosis-related genes plays an important role in the pathogenesis and therapeutic resistance in human cancer. In this study, we aimed to elucidate the role and mechanisms of resistance to apoptosis with caspase-8 gene downregulation in human malignant glioma. Reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP) were used to examine caspase-8 expressoin at the mRNA level and gene methylation status in normal brain tissue, glioma tissue and cancer cell lines. Caspase-8 protein kinase activity was measured by caspase-8 colorimetric assays; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining; the rates of tumor cell apoptosis were detected by flow cytometry. Our results revealed that caspase-8 gene silencing may result from the methylation of its gene promoter in human glioma tissues. The expression of caspase-8 at the mRNA level was significantly associated with the grade of human glioma. In certain human cancer cell lines, the expression at the mRNA level, protein kinase activity and tumor cell anti-apoptotic activity and resistance were related to the methylation status of the caspase-8 gene promoter. Thus, the caspase-8 gene methylation status may be used as an indicator for the early diagnosis of human malignant glioma. Combination therapy with demethylation reagents may overcome therapeutic resistance in the same malignancy.
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March-2017
Volume 39 Issue 3

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

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Spandidos Publications style
Teng Y, Dong YC, Liu Z, Zou Y, Xie H, Zhao Y, Su J, Cao F, Jin H, Ren H, Ren H, et al: DNA methylation-mediated caspase-8 downregulation is associated with anti-apoptotic activity and human malignant glioma grade. Int J Mol Med 39: 725-733, 2017.
APA
Teng, Y., Dong, Y., Liu, Z., Zou, Y., Xie, H., Zhao, Y. ... Ren, H. (2017). DNA methylation-mediated caspase-8 downregulation is associated with anti-apoptotic activity and human malignant glioma grade. International Journal of Molecular Medicine, 39, 725-733. https://doi.org/10.3892/ijmm.2017.2881
MLA
Teng, Y., Dong, Y., Liu, Z., Zou, Y., Xie, H., Zhao, Y., Su, J., Cao, F., Jin, H., Ren, H."DNA methylation-mediated caspase-8 downregulation is associated with anti-apoptotic activity and human malignant glioma grade". International Journal of Molecular Medicine 39.3 (2017): 725-733.
Chicago
Teng, Y., Dong, Y., Liu, Z., Zou, Y., Xie, H., Zhao, Y., Su, J., Cao, F., Jin, H., Ren, H."DNA methylation-mediated caspase-8 downregulation is associated with anti-apoptotic activity and human malignant glioma grade". International Journal of Molecular Medicine 39, no. 3 (2017): 725-733. https://doi.org/10.3892/ijmm.2017.2881