Abstract
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.
Highlights
Hepatocellular carcinoma (HCC, or hepatoma) is the most common primary malignancy of the liver in adults and the third leading cause of cancer-related deaths worldwide [1,2,3]
In accord with the apoptosis assay indicating, we found that the protein levels of caspase3, cleaved caspase3, cleaved caspase9 and cleaved PARP were strongly increased in hepatocellular carcinoma (HCC) cells treated with siCK2α as compared with the siNC group (Figure 8)
We found that CK2α was frequently and significantly up-regulated in human HCC at both the transcriptional (63.8%) and translational (70.9%) levels by RT-qPCR, Western blotting and IHC
Summary
Hepatocellular carcinoma (HCC, or hepatoma) is the most common primary malignancy of the liver in adults and the third leading cause of cancer-related deaths worldwide [1,2,3]. Progresses in the epidemiology, etiology, biology, diagnosis and treatment and prolonging postoperative survival have been substantial, the long-term prognosis of patients with HCC remains poor [6, 7]. These treatments have shown improvement in overall survival in early stage disease, but >70% of HCC patients who present with advanced disease would not benefit from them [3]. The crucial post-operative 5-year survival rate (30–40%) remains low and is an obstacle in the improvement of the prognosis for HCC patients [7]. As mechanisms of hepatocarcinogenesis are not completely understood, selecting novel molecular markers suitable for www.impactjournals.com/oncotarget early diagnosis and new therapeutic targets to improve the outcome of patients with HCC is crucial
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
