Loss of E-cadherin is associated with acquisition of metastatic capacity. 
Numerous studies suggest that histone deacetylation and/or hypermethylation of 
CpG islands in E-cadherin gene (CDH1) are major mechanisms responsible for 
E-cadherin silencing in different tumors and cancer cell lines. The hepatitis B 
virus (HBV)-encoded X antigen, HBx, contributes importantly to the development 
of hepatocellular carcinoma using multiple mechanisms. Experiments were designed 
to test if in addition to CDH1 hypermethylation HBx promotes epigenetic 
modulation of E-cadherin transcriptional activity through histone deacetylation 
and miR-373. The relationships between HBx, E-cadherin, mSin3A, Snail-1 and 
miR-373 were evaluated in HBx expressing (HepG2X) and control (HepG2CAT) cells 
by western blotting, immunoprecipitation (IP), chromatin IP as well as by 
immunohistochemical staining of liver and tumor tissue sections from 
HBV-infected patients. In HepG2X cells, decreased levels of E-cadherin and 
elevated levels of mSin3A and Snail-1 were detected. Reciprocal IP with anti-HBx 
and anti-mSin3A demonstrated mutual binding. Furthermore, HBx-mSin3A 
colocalization was detected by immunofluorescent staining. HBx downregulated 
E-cadherin expression by the recruitment of the mSin3A/histone deacetylase 
complex to the Snail-binding sites in human CDH1. Histone deacetylation 
inhibition by Trichostatin-A treatment restored E-cadherin expression. Mir-373, 
a positive regulator of E-cadherin expression, was downregulated by HBx in 
HepG2X cells and tissue sections from HBV-infected patients. Thus, histone 
deacetylation of CDH1 and downregulation of miR-373, together with the 
previously demonstrated hypermethylation of CDH1 by HBx, may be important for 
the understanding of HBV-related carcinogenesis.