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Open Access Research article

Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation

Jun Yan1, Qian Lu1, Jiahong Dong2*, Xiaowu Li1*, Kuansheng Ma1 and Lei Cai1

Author Affiliations

1 Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

2 Department of Hepatobiliary Surgery, PLA General Hospital, Beijing, 100853, China

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BMC Cancer 2012, 12:353  doi:10.1186/1471-2407-12-353

Published: 15 August 2012

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 (Pā€‰=ā€‰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 (Pā€‰=ā€‰0.001).

Conclusions

HBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.

Keywords:
Hepatitis B virus X protein; Hepatocellular carcinoma; Caveolin-1; Methylation