AccScience Publishing / TD / Online First / DOI: 10.36922/td.4571
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ORIGINAL RESEARCH ARTICLE

Deregulation of Casein Kinase-2 in non-small-cell lung cancer: A subunit-specific analysis

George V. Pérez1,2 ,  Chen Li3 ,  Chenyi Deng4 ,  Ying Yi5 ,  Qiang Zhao4 ,  Zhiwei Zhang3 ,  Wen Li5* ,  Silvio E. Perea1* ,  Yasser Perera1,5*
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1 Department of Pharmaceuticals, Biomedical Research Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba
2 Department of Biochemistry and Molecular Biology, Complutense, Madrid, Spain
3 Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute of Hengyang Medical School, University of South China, Hengyang, Hunan, People’s Republic of China
4 Department of Pathology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, People’s Republic of China
5 China-Cuba Biotechnology Joint Innovation Center, Yongzhou Development and Construction Investment Co., Ltd., Yongzhou, Hunan, People’s Republic of China
Tumor Discovery, 4571 https://doi.org/10.36922/td.4571
Submitted: 19 August 2024 | Accepted: 17 October 2024 | Published: 29 November 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Casein kinase-2 (CK2) is a constitutively active kinase that supports neoplastic properties. Although there is an extensive body of preclinical research on CK2, translational and clinical information remains limited and sparse. In this study, we interrogated clinical multiomics databases to examine CK2 deregulation across various cancers. Specifically, we analyzed the mutational frequency, copy-number alterations (CNA), and mRNA expression of CK2 catalytic (CSNK2A1 and CSNK2A2) and regulatory (CSNK2B) subunits across two major cancer genomic repositories (The Cancer Genome Atlas/International Cancer Genome Consortium). These genomic and transcriptomic analyses were further focused on lung cancer and complemented by in situ assessments of CK2 protein subunits and enzymatic activity in biopsies from non-small-cell lung cancer (NSCLC). Our findings indicate that gene mutations and CNA do not account for the elevated mRNA levels and enzymatic activity of CK2 subunits in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Particularly, the upregulation of CSNK2A1 and CSNK2B mRNA was associated with a worse prognosis and showed a direct correlation with the infiltration of myeloid-derived suppressor cells in LUAD. At the protein levels, all CK2 subunits and enzymatic activity were markedly elevated in LUAD (n = 103) and LUSC (n = 31) biopsies; however, only CSNK2A1 expression correlated positively with tumor size and disease stage. Finally, CSNK2A1 appeared to be more tumor-specific than CSNK2A2, suggesting that targeted therapies against this catalytic subunit or its homotetramer may offer a more favorable therapeutic window in NSCLC.

Keywords
Casein Kinase-2
Casein kinase-2 regulation
Lung cancer
Translational study
Oncology target
Funding
This research was supported by the National Key R&D Program of China (2021YFE0192100).
Conflict of interest
The authors declare that they have no competing interests.
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Tumor Discovery, Electronic ISSN: 2810-9775 Print ISSN: 3060-8597, Published by AccScience Publishing
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