Protein kinase CK2α catalytic subunit is overexpressed and serves as an unfavorable prognostic marker in primary hepatocellular carcinoma
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Hong-Xia Zhang1,2, Shan-Shan Jiang1,2, Xiao-Fei Zhang1,2, Zi-Qi Zhou1,2, Qiu-Zhong Pan1,2, Chang-Long Chen1,2, Jing-Jing Zhao1,2, Yan Tang1,2, Jian-Chuan Xia1,2, De-Sheng Weng1,2
1Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
2Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China
De-Sheng Weng, e-mail: [email protected]
Jian-Chuan Xia, e-mail: [email protected]
Keywords: CK2α, hepatocellular carcinoma, prognosis, oncogene, apoptosis
Received: April 14, 2015 Accepted: September 15, 2015 Published: September 25, 2015
Protein kinase CK2 alpha (CK2α), one isoform of the catalytic subunit of serine/threonine kinase CK2, has been indicated to participate in tumorigenesis of various malignancies. We conducted this study to investigate the biological significances of CK2α expression in hepatocellular carcinoma (HCC) development. Real-time quantitative polymerase and western blotting analyses revealed that CK2α expression was significantly increased at mRNA and protein levels in HCC tissues. Immunohistochemical analyses indicated that amplified expression of CK2α was highly correlated with poor prognosis. And functional analyses (cell proliferation and colony formation assays, cell migration and invasion assays, cell cycle and apoptosis assays) found that CK2α promoted cell proliferation, colony formation, migration and invasion, as well as inhibited apoptosis in hepatoma cell lines in vitro. CK2α-silenced resulted in significant apoptosis in cells that was demonstrated been associated with downregulation of expression of Bcl-2, p-AKT (ser473) and upregulation of expression of total P53, p-P53, Bax, caspase3 and cleaved-caspase3 in HCC cells. In addition, experiments with a mouse model revealed that the stimulative effect of CK2α on tumorigenesis in nude mice. Our results suggest that CK2α might play an oncogenic role in HCC, and therefore it could serve as a biomarker for prognostic and therapeutic applications in HCC.
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