非小细胞肺癌（NSCLC）在全球造成高死亡率。然而，其分子通路尚未被完全调查。FOXA1与CDC5L之间的关系及其在NSCLC中的作用尚未得到全面研究。从78名NSCLC患者收集了临床组织用于临床研究。BEAS-2B人类正常肺上皮细胞系以及A549、Calu-3、H526和H2170人类NSCLC细胞系被用于体外研究。sh-FOXA1和oe-CDC5L构建物被用于生成敲低和过表达模型。细胞活力分析采用CCK-8实验。细胞周期和凋亡通过流式细胞术分析进行评估。FOXA1和CDC5L之间的关系通过双荧光素酶和ChIP实验得以证明。通过免疫组织化学、qRT-PCR和Western blot分析检测了基因水平。NSCLC临床组织和细胞系中FOXA1水平增加。FOXA1耗竭增加细胞凋亡率，增加细胞进入G2/M期的比例。另外，我们证明了FOXA1直接结合至CDC5L启动子，而FOXA1的耗竭则抑制了CDC5L的表达。CDC5L的过表达诱导ERK1/2磷酸化，诱导JAK2磷酸化，抑制细胞凋亡，延长S期，并显著逆转了FOXA1敲低对NSCLC进展的影响。本研究证明了FOXA1通过上调CDC5L并激活ERK1/2和JAK2通路延长S期并促进NSCLC的进展。本研究由John Wiley & Sons Australia, Ltd代表高雄医学大学，由The Kaohsiung Journal of Medical Sciences出版。© 2023 作者 现代汉语

Non-small cell lung cancer (NSCLC) causes high mortality worldwide; however, its molecular pathways have not been fully investigated. The relationship between FOXA1 and CDC5L as well as their roles in NSCLC have not been comprehensively studied. Clinical tissues were collected from 78 NSCLC patients for clinical studies. The BEAS-2B human normal lung epithelial cell line and the A549, Calu-3, H526 and H2170 human NSCLC cell lines were used for in vitro studies. sh-FOXA1 and oe-CDC5L constructs were used to generate knockdown and overexpression models, respectively. The CCK-8 assay was used to analyze cell viability. The cell cycle and apoptosis were evaluated by flow cytometry analysis. The relationship between FOXA1 and CDC5L was demonstrated using dual-luciferase and ChIP assays. Gene levels were examined via immunohistochemistry, qRT-PCR and western blot analysis. FOXA1 levels were increased in NSCLC clinical tissues and cell lines. Depletion of FOXA1 increased the apoptosis rate and increased the proportion of cells in G2/M phase. In addition, we demonstrated that FOXA1 was directly bound to the promoter of CDC5L and that depletion of FOXA1 inhibited CDC5L expression. Overexpression of CDC5L induced ERK1/2 phosphorylation, induced JAK2 phosphorylation, inhibited cell apoptosis, prolonged S phase, and significantly reversed the effects of FOXA1 knockdown on the progression of NSCLC. The present study demonstrated that FOXA1 prolongs S phase and promotes NSCLC progression through upregulation of CDC5L and activation of the ERK1/2 and JAK2 pathways.© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.