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

BMC Cancer

Research Article

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

[1] Department of Hepatobiliary Surgery, PLA General Hospital, 100853, Beijing, China;Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, 400038, Chongqing, China;

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

DOI  :  10.1186/1471-2407-12-353

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

来源: Springer

【 摘 要 】

BackgroundTo understand the molecular mechanisms of caveolin-1 downregulation by hepatitis B virus X protein (HBx).MethodsThe 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.ResultsMethylation 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).ConclusionsHBx protein induces methylation of the caveolin-1 promoter region and suppresses its expression.

【 授权许可】

Unknown   
© Yan et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.