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<p>Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a key regulator of the cell cycle, but its role in neuroblastoma remains poorly understood. This study investigates the function and mechanisms of CKS2 in neuroblastoma through bioinformatics analyses, as well as in vitro and in vivo experiments. Data from the GEO and TCGA databases indicate that elevated <i>CKS2</i> expression is associated with poor prognosis in neuroblastoma. Analysis of clinical tumor samples and cell lines further confirmed that CKS2 was significantly overexpressed, particularly in high-risk neuroblastoma patient-derived tissues. Functional studies revealed that <i>CKS2</i> knockdown reduced cell proliferation and invasion, induced apoptosis, and caused cell cycle arrest in neuroblastoma cells. In vivo, tumors formed from <i>CKS2</i>-silenced cells showed markedly reduced growth. Mechanistically, <i>CKS2</i> knockdown decreased the phosphorylation of CDK1 (Thr161) and Cyclin B1 (Ser126), suggesting impaired cell division signaling. Treatment with importazole, an importin-β inhibitor, caused CKS2 to accumulate in the cytoplasm rather than in the nucleus, inhibiting proliferation and increasing apoptosis of neuroblastoma cells. Notably, the combination of <i>CKS2</i> knockdown and importazole treatment produced a stronger anti-tumor effect than either intervention alone. These findings demonstrate that CKS2 promotes neuroblastoma progression by facilitating cell division via the CDK1/Cyclin B1 complex. Targeting <i>CKS2</i>, especially in combination with nuclear import inhibition, offers a promising therapeutic strategy for neuroblastoma.</p>

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Nuclear Transport Receptor Importin-β Inhibition Enhances Cell Cycle Arrest Induced by CKS2 Knockdown to Suppress Neuroblastoma Progression

  • 期刊论文

  • 发表日期：

    2025年7月22日

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  • Shouhua Zhang,
  • Xiaozhen Meng,
  • Deng Xiang,
  • Hui Huang,
  • Yangfan Ge,
  • Yishan Zhan,
  • Kehao Li,
  • Xiaoyun Tan

摘要

Cyclin-dependent kinases regulatory subunit 2 (CKS2) is a key regulator of the cell cycle, but its role in neuroblastoma remains poorly understood. This study investigates the function and mechanisms of CKS2 in neuroblastoma through bioinformatics analyses, as well as in vitro and in vivo experiments. Data from the GEO and TCGA databases indicate that elevated CKS2 expression is associated with poor prognosis in neuroblastoma. Analysis of clinical tumor samples and cell lines further confirmed that CKS2 was significantly overexpressed, particularly in high-risk neuroblastoma patient-derived tissues. Functional studies revealed that CKS2 knockdown reduced cell proliferation and invasion, induced apoptosis, and caused cell cycle arrest in neuroblastoma cells. In vivo, tumors formed from CKS2-silenced cells showed markedly reduced growth. Mechanistically, CKS2 knockdown decreased the phosphorylation of CDK1 (Thr161) and Cyclin B1 (Ser126), suggesting impaired cell division signaling. Treatment with importazole, an importin-β inhibitor, caused CKS2 to accumulate in the cytoplasm rather than in the nucleus, inhibiting proliferation and increasing apoptosis of neuroblastoma cells. Notably, the combination of CKS2 knockdown and importazole treatment produced a stronger anti-tumor effect than either intervention alone. These findings demonstrate that CKS2 promotes neuroblastoma progression by facilitating cell division via the CDK1/Cyclin B1 complex. Targeting CKS2, especially in combination with nuclear import inhibition, offers a promising therapeutic strategy for neuroblastoma.