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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 / Copyright

    Affiliations: Department of Otorhinolaryngology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of General Sugery, General Hospital of Liaohe Oil Field, Panjin, Liaoning 124010, P.R. China, Department of Otorhinolaryngology, Fushun Second Hospital, Fushun, Liaoning 113001, P.R. China
  • Pages: 35-42
    |
    Published online on: November 3, 2014
       https://doi.org/10.3892/ol.2014.2662
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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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1 

Marioni G, Marchese-Ragona R, Cartei G, Marchese F and Staffieri A: Current opinion in diagnosis and treatment of laryngeal carcinoma. Cancer Treat Rev. 32:504–515. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Bugni JM, Meira LB and Samson LD: Alkylation-induced colon tumorigenesis in mice deficient in the Mgmt and Msh6 proteins. Oncogene. 28:734–741. 2009. View Article : Google Scholar

3 

Meng CF, Zhu XJ, Peng G and Dai DQ: Role of histone modifications and DNA methylation in the regulation of O6-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells. Cancer Invest. 28:331–339. 2010. View Article : Google Scholar

4 

McCabe MT, Brandes JC and Vertino PM: Cancer DNA methylation: molecular mechanisms and clinical implications. Clin Cancer Res. 15:3927–3937. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Kim YJ, Yoon HY, Kim SK, et al: EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling. Clin Cancer Res. 17:4523–4530. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Chang X, Li Z, Ma J, et al: DNA methylation of NDRG2 in gastric cancer and its clinical significance. Dig Dis Sci. 58:715–723. 2013. View Article : Google Scholar

7 

Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y and Futscher BW: 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 26:77–90. 2007. View Article : Google Scholar

8 

Sharma S, Kelly TK and Jones PA: Epigenetics in cancer. Carcinogenesis. 31:27–36. 2010. View Article : Google Scholar :

9 

O’Sullivan B and Shah J: New TNM staging criteria for head and neck tumors. Semin Surg Oncol. 21:30–42. 2003. View Article : Google Scholar

10 

Samudio-Ruiz SL and Hudson LG: Increased DNA methyltransferase activity and DNA methylation following epidermal growth factor stimulation in ovarian cancer cells. Epigenetics. 7:216–224. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Kondo Y, Shen L, Cheng AS, et al: Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet. 40:741–750. 2008. View Article : Google Scholar : PubMed/NCBI

12 

Socha MJ, Said N, Dai Y, et al: Aberrant promoter methylation of SPARC in ovarian cancer. Neoplasia. 11:126–135. 2009.PubMed/NCBI

13 

Wu LP, Wang X, Li L, et al: Histone deacetylase inhibitor depsipeptide activates silenced genes through decreasing both CpG and H3K9 methylation on the promoter. Mol Cell Biol. 28:3219–3235. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Grewal SI and Moazed D: Heterochromatin and epigenetic control of gene expression. Science. 301:798–802. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Chang X, Zhang S, Ma J, et al: Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens. Cell Biochem Biophys. 66:93–101. 2013. View Article : Google Scholar

16 

Agathanggelou A, Cooper WN and Latif F: Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res. 65:3497–3508. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Fahrner JA, Eguchi S, Herman JG and Baylin SB: Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 62:7213–7218. 2002.PubMed/NCBI

18 

Liu J, Zhu X, Xu X and Dai D: DNA promoter and histone H3 methylation downregulate NGX6 in gastric cancer cells. Med Oncol. 31:8172014. View Article : Google Scholar

19 

Dong W, Wang L and Shen R: MYO5B is epigenetically silenced and associated with MET signaling in human gastric cancer. Dig Dis Sci. 58:2038–2045. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Chakraborty AK, de Sousa JF, Chakraborty D, et al: GnT-V expression and metastatic phenotypes in macrophage-melanoma fusion hybrids is down-regulated by 5-Aza-dC: evidence for methylation sensitive, extragenic regulation of GnT-V transcription. Gene. 374:166–173. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Peng DF, Razvi M, Chen H, et al: DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett’s adenocarcinoma. Gut. 58:5–15. 2009. View Article : Google Scholar

22 

Fuks F, Hurd PJ, Deplus R and Kouzarides T: The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31:2305–2312. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Lin W and Dent SY: Functions of histone-modifying enzymes in development. Curr Opin Genet Dev. 16:137–142. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Kondo Y: Epigenetic cross-talk between DNA methylation and histone modifications in human cancers. Yonsei Med J. 50:455–463. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Schneider BG, Peng DF, Camargo MC, et al: Promoter DNA hypermethylation in gastric biopsies from subjects at high and low risk for gastric cancer. Int J Cancer. 127:2588–2597. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Tost J: DNA methylation: an introduction to the biology and the disease-associated changes of a promising biomarker. Methods Mol Biol. 507:3–20. 2009. View Article : Google Scholar

27 

Tong JD, Jiao NL, Wang YX, Zhang YW and Han F: Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis. Neoplasma. 58:441–448. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Zhi Y, Chen J, Zhang S, et al: Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci. 57:650–659. 2012. View Article : Google Scholar

29 

Hu Q, Yu L, Chen R, Wang YL, et al: 5-aza-2′-deoxycytidine improves the sensitivity of endometrial cancer cells to progesterone therapy. Int J Gynecol Cancer. 22:951–959. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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