Bioinformatics Study on Proliferation,Invasion and Migration of FOXD1 Regulated by PI3K/AKT in Lung Squamous Carcinoma

ZHAO Erlin; DU Yongmei; XIAO Xuyang

doi:10.3969/j.issn.2096-305X.2025.02.002

Abstract：Objective This study aims to analyze the expression characteristics of the transcription factor FOXD1 in lung squamous cell carcinoma(LUSC)using bioinformatics methods and explore its potential impact on cell proliferation,invasion,and migration in LUSC.Methods Gene expression data from LUSC patients were obtained from the public databases TCGA and UALCAN.FOXD1 expression was analyzed in relation to different clinical stages and survival outcomes.small interfering RNA(siRNA)technology was used to silence FOXD1,while plasmid transfection was employed to overexpress FOXD1.The effects of FOXD1 on LUSC cell proliferation,migration,and invasion were evaluated using CCK-8,scratch wound healing,and Transwell assays.Results Bioinformatics analysis revealed that FOXD1 expression was significantly upregulated in LUSC tissues,and its high expression was strongly associated with poor patient prognosis.CCK-8 assays showed that silencing FOXD1 significantly inhibited cell proliferation,whereas overexpression promoted proliferation.Scratch wound healing and Transwell assays further demonstrated that FOXD1 silencing significantly reduced cell migration and invasion,while its overexpression enhanced these capabilities.Western Blot analysis indicated a significant decrease in the activation of the PI3K/AKT signaling pathway in the FOXD1 knockdown group,suggesting that FOXD1 may promote cell proliferation and invasion through activation of this pathway.In the FOXD1 overexpression group,PI3K/AKT pathway activation was markedly increased,further confirming the pivotal role of FOXD1 in regulating tumor cell biological behaviors.Conclusion FOXD1 is highly expressed in LUSC and affects its malignant features by promoting cell proliferation,invasion,and migration.FOXD1 may regulate LUSC biological behaviors via the PI3K/AKT signaling pathway,indicating its potential as a therapeutic target for LUSC.Further studies are needed to investigate the underlying mechanisms.