Epigenetic regulation of hTERT promoter in hepatocellular carcinomas

  • Authors:
    • Dimitrios Iliopoulos
    • Maria Satra
    • Alexandra Drakaki
    • George A. Poultsides
    • Aspasia Tsezou
  • View Affiliations

  • Published online on: Sunday, February 1, 2009
  • Pages: 391-399
  • DOI: 10.3892/ijo_00000162

Abstract

Although hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, the molecular pathogenesis of the disease has not been elucidated. Several studies have shown that telomerase activity and hTERT expression are increased in HCCs. In the present study we tried to elucidate hTERT transcriptional and epigenetic regulatory mechanisms in HCC. hTERT expression was tested by real-time PCR and DNA methylation status was assessed by MethyLight and DNA bisulfite sequencing analyses in 106 tissues (64 with HCC and 42 without liver disorders) and also in 7 hepatocarcinoma cell lines (HepG2, HepG3B2, C3A, SNU-182, SNU-398, SBU-449 and SNU-475). hTERT expression levels were inversely correlated with DNA methylation levels in HCC and normal tissues (r=−0.859). hTERT expression was found to be regulated by DNA methylation and histone H3-K9 modifications, affecting the ability of c-myc binding in E-box 1 site in hTERT promoter. Additionally, c-myc siRNA liposomal down-regulation inhibited significantly hTERT expression (p<0.05). Thus, we propose that hTERT is regulated by a combination of epigenetic mechanisms (DNA methylation and histone modifications) and by the transcription factor c-myc in HCC.
Journal Cover

February 2009
Volume 34 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Iliopoulos, D., Satra, M., Drakaki, A., Poultsides, G., & Tsezou, A. (2009). Epigenetic regulation of hTERT promoter in hepatocellular carcinomas. International Journal of Oncology, 34(2), 391-399.
MLA
Iliopoulos, Satra, Drakaki, Poultsides, and Aspasia Tsezou. "Epigenetic regulation of hTERT promoter in hepatocellular carcinomas." International Journal of Oncology International Journal of Oncology 34.2 (2009): 391-399.
Chicago
Iliopoulos, Satra, Drakaki, Poultsides, and Aspasia Tsezou. "Epigenetic regulation of hTERT promoter in hepatocellular carcinomas." International Journal of Oncology International Journal of Oncology 34 no. 2 (2009): 391-399.