Lu Xiao-Ning, Chen Jun, Han Guang, Ding Cheng, Li Chang, Xu Chun, Cui Yuan, Ju Sheng, Tong Xin, Zhao Jun
Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Curr Med Sci. 2025 May 28. doi: 10.1007/s11596-025-00055-x.
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality. This study aimed to investigate the role of checkpoint kinase 1 (CHEK1) in NSCLC progression and its regulatory relationship with forkhead box protein M1 (FOXM1).
Transwell assays were used to evaluate the migration and invasion capabilities of NSCLC cells with either CHEK1 overexpression or knockdown. The expression of epithelial-mesenchymal transition (EMT) markers in NSCLC cells under CHEK1 overexpression or knockdown conditions was analyzed via Western blotting. Proliferative capacity was assessed using CCK-8 assays in NSCLC cells with modulated CHEK1 expression. Additionally, real-time quantitative PCR was employed to measure CHEK1 and FOXM1 expression levels in NSCLC tissues. The effects of CHEK1 knockdown on tumor growth were further validated in animal models. The binding of FOXM1 to the CHEK1 promoter region was examined using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays.
FOXM1 and CHEK1 were upregulated in NSCLC tissues. CHEK1 overexpression promoted NSCLC cell proliferation, while its knockdown suppressed proliferation, inhibited EMT, and reduced tumor growth in vivo. FOXM1 was shown to directly bind to CHEK1 promoter, thereby upregulating CHEK1 expression.
CHEK1 promotes NSCLC cell proliferation and tumor growth, and its expression is regulated by FOXM1. These findings suggest CHEK1 and FOXM1 are potential therapeutic targets for NSCLC treatment.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因。本研究旨在探讨检查点激酶1（CHEK1）在NSCLC进展中的作用及其与叉头框蛋白M1（FOXM1）的调控关系。
采用Transwell实验评估CHEK1过表达或敲低的NSCLC细胞的迁移和侵袭能力。通过蛋白质免疫印迹法分析CHEK1过表达或敲低条件下NSCLC细胞中上皮-间质转化（EMT）标志物的表达。使用CCK-8实验评估CHEK1表达被调控的NSCLC细胞的增殖能力。此外，采用实时定量PCR检测NSCLC组织中CHEK1和FOXM1的表达水平。在动物模型中进一步验证敲低CHEK1对肿瘤生长的影响。使用双荧光素酶报告基因实验和染色质免疫沉淀（ChIP）实验检测FOXM1与CHEK1启动子区域的结合情况。
NSCLC组织中FOXM1和CHEK1上调。CHEK1过表达促进NSCLC细胞增殖，而敲低CHEK1则抑制增殖、抑制EMT并减少体内肿瘤生长。结果表明FOXM1直接结合CHEK1启动子，从而上调CHEK1表达。
CHEK1促进NSCLC细胞增殖和肿瘤生长，其表达受FOXM1调控。这些发现表明CHEK1和FOXM1是NSCLC治疗潜在的治疗靶点。
