Zhang Hong-Xia, Jiang Shan-Shan, Zhang Xiao-Fei, Zhou Zi-Qi, Pan Qiu-Zhong, Chen Chang-Long, Zhao Jing-Jing, Tang Yan, Xia Jian-Chuan, Weng De-Sheng
Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Oncotarget. 2015 Oct 27;6(33):34800-17. doi: 10.18632/oncotarget.5470.
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.
蛋白激酶CK2α(CK2α)是丝氨酸/苏氨酸激酶CK2催化亚基的一种同工型,已被表明参与多种恶性肿瘤的肿瘤发生过程。我们开展本研究以探究CK2α表达在肝细胞癌(HCC)发生发展中的生物学意义。实时定量聚合酶链反应和蛋白质印迹分析显示,HCC组织中CK2α在mRNA和蛋白质水平上均显著升高。免疫组织化学分析表明,CK2α的扩增表达与不良预后高度相关。功能分析(细胞增殖和集落形成试验、细胞迁移和侵袭试验、细胞周期和凋亡试验)发现,CK2α在体外促进肝癌细胞系的细胞增殖、集落形成、迁移和侵袭,并抑制细胞凋亡。CK2α沉默导致细胞显著凋亡,这与HCC细胞中Bcl-2、p-AKT(ser473)表达下调以及总P53、p-P53、Bax、caspase3和裂解的caspase3表达上调有关。此外,小鼠模型实验揭示了CK2α对裸鼠肿瘤发生的刺激作用。我们的结果表明,CK2α可能在HCC中发挥致癌作用,因此它可作为HCC预后和治疗应用的生物标志物。