Aberrant expression of CKS2 induced by ELK1 contributes to malignant progression of pancreatic cancer.

Qiuyang Chen, Yue Fu, Xinchun Liu, Peng Wang, Shangnan Dai, Feng Zhu, Tongtai Liu, Wenbin Xu, Junli Wu

Molecular carcinogenesis 2023 Dec

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Cyclin-dependent kinase subunit 2 (CKS2) has been reported to promote various malignancies. This study investigated the functional role of CKS2 in pancreatic cancer (PC). An analysis of abnormally expressed genes and their prognostic value for PC was performed by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and performing immunohistochemical staining on 64 samples of tumor tissue. CCK-8 assays, EdU staining, colony formation assays, flow cytometry, and a xenograft tumor model were used to analyze the biological function of CKS2 in PC. Our results revealed that CKS2 was expressed at significantly higher levels in PC tissues than in adjacent normal tissues, and a high level of CKS2 expression was associated with a poor prognosis for patients with PC. Moreover, functional assays revealed that CKS2 knockdown suppressed cell proliferation, induced cell cycle S phase, G2/M phase arrest, and apoptosis in vitro, and also reduced tumor growth in vivo. In addition, CKS2 knockdown increased the levels of Bax, caspase-3, P53, P21, and GADD45α expression, but decreased Bcl-2, Cyclin B1, CDK1, Cyclin A, and Cdc25C expression. CKS2 overexpression produced the opposite effects of CKS2 knockdown. Furthermore, we found that ELK1 protein regulated transcription of the CKS2 gene. In conclusion, our findings suggest that CKS2 expression is regulated by ELK1, which could possibly serve as prognostic indicator and therapeutic target for PC. © 2023 Wiley Periodicals LLC.

Citation

Qiuyang Chen, Yue Fu, Xinchun Liu, Peng Wang, Shangnan Dai, Feng Zhu, Tongtai Liu, Wenbin Xu, Junli Wu. Aberrant expression of CKS2 induced by ELK1 contributes to malignant progression of pancreatic cancer. Molecular carcinogenesis. 2023 Dec;62(12):1947-1959