DNA methyltransferases (DNMTs) are essential for maintenance of aberrant 
methylation in cancer cells and play important roles in the development of 
cancers. Unregulated activation of PI3K/Akt pathway is a prominent feature of 
many human cancers including human hepatocellular carcinoma (HCC). In present 
study, we found that DNMT3B mRNA and protein levels were decreased in a dose- 
and time-dependent manner in HCC cell lines with LY294002 treatment. However, we 
detected that LY294002 treatment did not induce increase of the degradation of 
DNMT3B protein using protein decay assay. Moreover we found that Akt induced 
alteration of the expression of DNMT3B in cells transfected with myristylated 
variants of Akt2 or cells transfected with small interfering RNA respectively. 
Based on DNMT3B promoter dual-luciferase reporter assay, we found PI3K pathway 
regulates DNMT3B expression at transcriptional level. And DNMT3B mRNA decay 
analysis suggested that down-regulation of DNMT3B by LY294002 is also 
post-transcriptional control. Furthermore, we demonstrated that LY294002 
down-regulated HuR expression in a time-dependent manner in BEL-7404. In 
summary, we have, for the first time, demonstrate that PI3K/Akt pathway 
regulates the expression of DNMT3B at transcriptional and post-transcriptional 
levels, which is particularly important to understand the effects of PI3K/Akt 
and DNMT3B on hepatocarcinogenesis.