CDK5 targets p21CIP1 to regulate thyroid cancer cell proliferation and malignancy in patients.

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.