Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

The molecular mechanisms underlying hepatitis B virus encoded HBx protein -mediated tumorigenesis are not fully understood. In order to gain a better view of the effects of HBx on transcriptional regulation and hepatocarcinogenesis, the expression profiles of liver and tumor tissues from 6 and 18 month-old p21-HBxtransgenic and control mice were monitored using oligo microarrays. Data analysis demonstrated that 42 genes were de-regulated in both 6 and 18 month-old HBxtransgenic mouse tissues. Gene ontology assisted analysis classified these genes into functionally related clusters that encode proteins related to metabolism, signal transduction, transcription regulation and stress responses. Among them, cytoskeletal genes, including microtubule genes tubulin-β2 (Tubb2), tubulin-β3 (Tubb3) and tubulin-β6 (Tubb6) , intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and actin-γ1 (Actg1) , were closely clustered and up-regulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The up-regulation of K8 and K18was only detected in p21-HBxbut not p21-HBsAgliver tissues, suggesting that the global change in the expression of cellular cytoskeletal genes was correlated with the expression of HBxtransgene. These findings propose for the first time that systemic dysregulation of cellular cytoskeletal genes is involved in HBx–induced hepatocarcinogenesis.