Hepatitis B virus X protein suppresses caveolin-1 expression in hepatocellular carcinoma by regulating DNA methylation.
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.
Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Jun
J
Yan
Qian
Q
Lu
Jiahong
J
Dong
Xiaowu
X
Li
Kuansheng
K
Ma
Lei
L
Cai
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D008297:Male; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D051242:Caveolin 1; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein