Histone deacetylase 2 (HDAC2) is aberrantly regulated and plays a pivotal role in the development of hepatocellular carcinoma (HCC) through regulation of cell-cycle components at the transcriptional level, but the underlying mechanism leading to oncogenic HDAC2 remains unknown. In this study, we show that expression of CK2a (casein kinase II a subunit) was up-regulated in a large cohort of human HCC patients, and that high expression of CK2a was significantly associated with poor prognosis of HCC patients in terms of five-year overall survival. It was also found that CK2a over-expression positively correlated with HDAC2 over-expression in a subset of HCCs. We observed that treatment with epidermal growth factor (EGF) elicited an increase in CK2a expression and Akt phosphorylation, causing induction of HDAC2 expression in liver cancer cells. It was also observed that ectopic expression of dominant-negative CK2a blocked EGF-induced HDAC2 expression, and that ectopic CK2a expression attenuated the suppressive effect of Akt knockdown on HDAC2 expression in liver cancer cells. Targeted disruption of CK2a influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G 2 /M phase, and suppressed growth via repression of Cdc25c and cyclin B in liver cancer cells. Taken together, our findings suggest the oncogenic potential of CK2a in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC2 expression is proposed whereby EGF induces transcriptional activation of HDAC2 by CK2a/Akt activation in liver cancer cells. Therefore, this makes CK2a a promising target in cancer therapy.

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