Oncogenic potential of CK2[alpha] and its regulatory role in EGF-induced HDAC2 expression in human liver cancer

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 CK2[alpha] (casein kinase II [alpha] subunit) was up-regulated in a large cohort of human HCC patients, and that high expression of CK2[alpha] was significantly associated with poor prognosis of HCC patients in terms of five-year overall survival. It was also found that CK2[alpha] 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 CK2[alpha] expression and Akt phosphorylation, causing induction of HDAC2 expression in liver cancer cells. It was also observed that ectopic expression of dominant-negative CK2[alpha] blocked EGF-induced HDAC2 expression, and that ectopic CK2[alpha] expression attenuated the suppressive effect of Akt knockdown on HDAC2 expression in liver cancer cells. Targeted disruption of CK2[alpha] influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G2/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 CK2[alpha] in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC2 expression is proposed whereby EGF induces transcriptional activation of HDAC2 by CK2[alpha]/Akt activation in liver cancer cells. Therefore, this makes CK2[alpha] a promising target in cancer therapy. [PUBLICATION ABSTRACT]