Open Access

Clinical significance of epigenetic silencing and re‑expression of O6‑methylguanine‑DNA methyltransferase using epigenetic agents in laryngeal carcinoma

  • Authors:
    • Jing Yang
    • Xin‑Bing Zhu
    • Li‑Xia He
    • Zhao‑Wei Gu
    • Ming‑Zhu Jin
    • Wen‑Yue Ji
  • View Affiliations

  • Published online on: November 3, 2014     https://doi.org/10.3892/ol.2014.2662
  • Pages: 35-42
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Abstract

The aim of the present study was to investigate the association between O6‑methylguanine‑DNA methyltransferase (MGMT) gene expression levels, and DNA methylation status and histone modifications in laryngeal squamous cell carcinoma (LSCC). Chromatin immunoprecipitation, methylation‑specific polymerase chain reaction (PCR), and reverse transcription‑quantitative PCR were performed to analyze histone modifications, DNA methylation status and mRNA expression levels in the promoter region of the MGMT gene in laryngeal carcinoma HEp‑2 cells, as well as in 50 paired healthy and LSCC tissue samples. The present study demonstrated that treatment of HEp‑2 cells with 5‑aza‑2'‑deoxycytidine (Aza), a DNA methyltransferase inhibitor, significantly upregulated MGMT mRNA expression levels, reduced MGMT DNA methylation, reduced MGMT histone H3 lysine 9 (H3K9) di‑methylation, and increased MGMT histone H3 lysine 4 di‑methylation without a significant change in H3K9 acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, marginally upregulated MGMT mRNA expression levels without affecting the DNA methylation status, or H3K9 or H3K4 di‑methylation, however, TSA treatment caused a significant increase in H3K9 acetylation. Furthermore, Aza and TSA combination treatment produced a synergistic effect. In the LSCC samples, the rate of DNA methylation in the MGMT gene was 54%, compared with 24% in the healthy control group (P<0.05). Therefore, data from the present study indicates that MGMT may serve as a novel therapeutic target in the treatment of LSCC.
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January-2015
Volume 9 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Yang J, Zhu XB, He LX, Gu ZW, Jin MZ and Ji WY: Clinical significance of epigenetic silencing and re‑expression of O6‑methylguanine‑DNA methyltransferase using epigenetic agents in laryngeal carcinoma. Oncol Lett 9: 35-42, 2015
APA
Yang, J., Zhu, X., He, L., Gu, Z., Jin, M., & Ji, W. (2015). Clinical significance of epigenetic silencing and re‑expression of O6‑methylguanine‑DNA methyltransferase using epigenetic agents in laryngeal carcinoma. Oncology Letters, 9, 35-42. https://doi.org/10.3892/ol.2014.2662
MLA
Yang, J., Zhu, X., He, L., Gu, Z., Jin, M., Ji, W."Clinical significance of epigenetic silencing and re‑expression of O6‑methylguanine‑DNA methyltransferase using epigenetic agents in laryngeal carcinoma". Oncology Letters 9.1 (2015): 35-42.
Chicago
Yang, J., Zhu, X., He, L., Gu, Z., Jin, M., Ji, W."Clinical significance of epigenetic silencing and re‑expression of O6‑methylguanine‑DNA methyltransferase using epigenetic agents in laryngeal carcinoma". Oncology Letters 9, no. 1 (2015): 35-42. https://doi.org/10.3892/ol.2014.2662