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

BMC Cancer

Jun Yan²  Qian Lu²  Jiahong Dong¹  Xiaowu Li²  Kuansheng Ma²  Lei Cai² 

[1] Department of Hepatobiliary Surgery, PLA General Hospital, Beijing, 100853, China

[2] Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

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

Others  :  1080255
DOI  :  10.1186/1471-2407-12-353

 received in 2012-01-17, accepted in 2012-08-09,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Yan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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