Abstract
Background
Aberrant CpG island hypermethylation is a major epigenetic mechanism that can inactivate the transcription of cancer-related genes.
Purpose
This study aimed to investigate whether Oct-6 transcription was regulated by CpG island methylation in hepatocellular carcinoma (HCC).
Methods
Quantitative real-time PCR and the MassARRAY platform (Sequenom) were employed in 38 HCC tissues samples and four cell lines.
Results
The levels of Oct-6 mRNA were decreased by more than twofold in 31 of 38 tumor tissues compared to that of adjacent non-cancerous tissues. Among the 31 tumor tissues with lower levels of Oct-6 mRNA, 17 tumor tissues also had higher methylation levels in Oct-6 CpG island. Based on these results, we hypothesized that CpG island hypermethylation may down-regulate Oct-6 mRNA expression in HCC. To confirm this hypothesis, we also analyzed the changes in Oct-6 mRNA expression and CpG island methylation in four HCC cell lines (Huh7, Bel-7402, HepG2 and SMMC-7721) after treatment with 0.1, 0.5 and 2.5 μM 5-Aza-2-deoxycytidine (5-Aza-CdR), a demethylating agent. The results demonstrated that the CpG island methylation levels decreased and Oct-6 mRNA levels increased in a dose-dependent manner in both Huh7 and Bel7402 cells, but there were only slight changes in HepG2 cell. Interestingly, there were no significant alterations of Oct-6 mRNA levels observed in SMMC7721 cell; although lower levels of CpG island methylation were detected after treatment with 5-Aza-CdR.
Conclusions
Our study shows that CpG island hypermethylation contributes to down-regulation of Oct-6 mRNA expression in HCC.
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Acknowledgments
This work was supported by Key Programs for Science and Technology Development of Guangzhou (Grant no. 2008A1-E4151) and the National High Technology Research and Development Program of China (Grant no. 2006AA02A311).
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Jing-zhe Sun and Xue-xi Yang contributed equally to this study.
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Sun, Jz., Yang, Xx., Li, Xh. et al. Aberrant CpG Island Hypermethylation and Down-Regulation of Oct-6 mRNA Expression in Human Hepatocellular Carcinoma. Dig Dis Sci 56, 3072–3077 (2011). https://doi.org/10.1007/s10620-011-1686-y
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DOI: https://doi.org/10.1007/s10620-011-1686-y