CDK1 depletion suppresses glioma malignancy through cell cycle pathway regulation: Mechanistic insights from functional and molecular profiling

Glioblastoma remains a lethal malignancy with limited therapeutic advancements. Emerging evidence implicates cell cycle dysregulation in glioma pathogenesis, yet the mechanistic role of cyclin‑dependent kinase 1 (CDK1) remains underexplored. The present study systematically evaluated the clinical relevance and functional impact of CDK1 in glioma progression through multi‑modal experimental approaches. CDK1 expression was analyzed using public datasets and then verified by western blotting using patient tissue samples (n=37) from the Second Hospital of Hebei Medical University (Shijiazhuang, China). Survival analysis was performed using Chinese Glioma Genome Atlas and The Cancer Genome Atlas datasets, alongside multivariate Cox regression to evaluate prognostic independence. Functional assays, including small interfering RNA‑mediated CDK1 knockdown, were conducted in glioma cell lines to assess proliferation (Cell Counting Kit‑8 and EdU), migration/invasion (Transwell), apoptosis (acridine orange/ethidium bromide staining and flow cytometry) and radiosensitivity (γ‑H2AX foci quantification post‑irradiation). The expression levels of downstream cell cycle regulators were quantified via quantitative PCR. The results indicated that CDK1 was significantly upregulated in glioma tissues compared with normal controls, with expression levels escalating with tumor grade. High CDK1 expression correlated with a reduced overall survival and served as an independent prognostic marker. CDK1 knockdown attenuated glioma cell proliferation, migration and invasion, while enhancing apoptosis and radiosensitivity. Mechanistically, CDK1 knockdown downregulated cell cycle regulators proliferating cell nuclear antigen, minichromosome maintenance complex component 2‑4 (MCM2‑4), MCM6, polo‑like kinase 1, TTK protein kinase and mitotic arrest deficient 2 like 1, implicating mitotic dysregulation as a central pathway. The present study established CDK1 as a master regulator of glioma progression through coordinated control of proliferation, DNA repair and metastatic potential. The robust association between CDK1 expression, tumor grade and survival, coupled with functional validation across complementary assays, positions CDK1 inhibition as a promising therapeutic strategy. The mechanistic elucidation of its cell cycle network provides a novel framework for targeting glioma‑specific therapeutic targets.