Aberrant CpG island hypermethylation and down-regulation of Oct-6 mRNA expression in human hepatocellular carcinoma.
Dig Dis Sci
; 56(10): 3072-7, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21448695
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
DNA de Neoplasias
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RNA Mensageiro
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Regulação para Baixo
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Carcinoma Hepatocelular
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Ilhas de CpG
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Metilação de DNA
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Fator 6 de Transcrição de Octâmero
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Neoplasias Hepáticas
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article