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Background: The hepatitis B virus x gene (HBx) is a promiscuous transactivator implicated in the development of hepatocellular carcinoma (HCC). The present study was designed to investigate the molecular events regulated byHBx.Methods: Genomic and proteomic expression profiling was performed in Huh7 HCC cells transfected withHBxmutants with a C-terminal deletion. The gene and protein expression of wingless-type murine-mammary-tumour virus (MMTV) integration site family, member 5A (Wnt-5a) was validated by analyses of reverse transcription–polymerase chain reaction (RT–PCR), real-time RT–PCR, western blot and immunohistochemistry.Results: Differentially expressed genes and proteins were found in the transfected Huh7 HCC cells; most of them were involved in transcriptional regulation, although others including oncogenes or tumor suppressor genes, and molecules involved in cell junctions, signal transduction pathways, metabolism or the immune response were also observed. The expression of theWnt-5agene was elevated &gt;10-fold in Huh7 cells transfected with theHBx3′-30 amino acid deletion mutant. However, the expression was downregulated by the transfection with theHBx3′-40 amino acid deletion mutant. The changes in Wnt-5a expression were also observed in human HCC tissues, compared with corresponding non-cancerous liver tissues. A negative correlation was found between the expression of Wnt-5a andHBxCOOH mutations in HCC tissues.Conclusions:HBxmutants may participate in the development and progression of HCC, at least in part through the Wnt-5a pathway.

carcinogenesis

Mutations in the C-terminus of the X protein of hepatitis B virus regulate Wnt-5a expression in hepatoma Huh7 cells: cDNA microarray and proteomic analyses