CDK5 targets p21<sup>CIP1</sup> to regulate thyroid cancer cell proliferation and malignancy in patients

Tung,Min-Che; Oner,Muhammet; Soong,Shiuan-Woei; Cheng,Pang-Ting; Li,Yu-Hsuan; Chen,Mei-Chih; Chou,Chen-Kai; Kang,Hong-Yo; Lin,Frank Cheau-Feng; Tsai,Stella Chin-Shaw; Lin,Ho

doi:10.3892/mmr.2025.13547

CDK5 targets p21^CIP1 to regulate thyroid cancer cell proliferation and malignancy in patients

Authors:
- Min-Che Tung
- Muhammet Oner
- Shiuan-Woei Soong
- Pang-Ting Cheng
- Yu-Hsuan Li
- Mei-Chih Chen
- Chen-Kai Chou
- Hong-Yo Kang
- Frank Cheau-Feng Lin
- Stella Chin-Shaw Tsai
- Ho Lin
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Affiliations: Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung 43503, Taiwan, R.O.C., Department of Life Sciences, National Chung Hsing University, Taichung 40227, Taiwan, R.O.C., Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan, R.O.C., Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan, R.O.C., Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan 83301, Taiwan, R.O.C., School of Medicine, Chung Shan Medical University, Taichung 402367, Taiwan, R.O.C., Department of Otolaryngology, Tungs' Taichung MetroHarbor Hospital, Taichung 43503, Taiwan, R.O.C.
Published online on: April 24, 2025 https://doi.org/10.3892/mmr.2025.13547
Article Number: 182
Copyright: © Tung et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cyclin‑dependent kinase 5 (CDK5), known for its role in neuronal function, has emerged as a key player in cancer biology, particularly in thyroid cancer. The present study explored the interaction between CDK5 and the cyclin‑dependent kinase inhibitor p21^CIP1 in thyroid cancer (TC). Bioinformatic tools and immunoprecipitation assays were used to confirm that CDK5 targets p21 for ubiquitin‑mediated degradation, reducing its stability and tumor‑suppressive effects. Data from The Cancer Genome Atlas revealed a significant inverse correlation between CDK5 and p21 expression, with higher CDK5 levels linked to increased tumor malignancy and worse survival outcomes; conversely, higher p21 expression was correlated with an improved prognosis. Immunohistochemistry analysis of TC samples further confirmed that increased CDK5 and reduced p21 expression were associated with more advanced tumor stages and aggressive phenotypes. These findings suggested that CDK5‑mediated degradation of p21 contributes to TC progression and malignancy, highlighting the potential of targeting the CDK5‑p21 axis as a therapeutic strategy for management of TC.

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