Published in:
Open Access
01-12-2012 | Research article
Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation
Authors:
Jun Yan, Qian Lu, Jiahong Dong, Xiaowu Li, Kuansheng Ma, Lei Cai
Published in:
BMC Cancer
|
Issue 1/2012
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Abstract
Background
To understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).
Methods
The DNA methylation status of the caveolin-1 promoter was examined by nested methylation-specific PCR of 33 hepatitis B virus (HBV)-infected hepatocellular carcinoma (HCC) samples. The SMMC-7721 hepatoma cell line was transfected with a recombinant HBx adenoviral vector, and the effects of HBx protein on caveolin-1 expression and promoter methylation were examined and confirmed by sequencing. A reporter gene containing the caveolin-1 promoter region was constructed, and the effects of HBx on the transcriptional activity of the promoter were also studied.
Results
Methylation of the caveolin-1 promoter was detected in 84.8% (28/33) of HBV-infected HCC samples. Expression of caveolin-1 was significantly downregulated (P = 0.022), and multiple CpG sites in the promoter region of caveolin-1 were methylated in SMMC-7721 cells after HBx transfection. Transfected HBx significantly suppressed caveolin-1 promoter activity (P = 0.001).
Conclusions
HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.