Abstract

Background Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide, highlighting the urgent need for additional molecular biomarkers and therapeutic targets. Transcription factor AP-2α (TFAP2A) is highly expressed in LUAD and is associated with poor prognosis. Sphingosine-1-phosphate phosphatae 2 (SGPP2/SPP2) has been implicated in tumor progression in multiple cancer types; however, its functional role in LUAD cells and the underlying mechanisms remain unclear. Methods Bioinformatics analysis was conducted to elucidate the expression patterns of SGPP2 and TFAP2A. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were performed to measure mRNA and protein expression levels. Cellular proliferation and cell cycle progression were evaluated using the Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2’-deoxyuridine (EdU) assay, colony formation assay, and flow cytometry. Migratory and invasive capabilities were evaluated using transwell and wound-healing assays. Lipid metabolism was assessed by measuring triglyceride (TG) and total cholesterol (TC) levels, using Oil Red O and Nile Red fluorescence staining. The regulatory relationship between TFAP2A and the SGPP2 promoter was confirmed using chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. Protein-protein interactions were investigated using co-immunoprecipitation (CoIP) assay. The in vivo tumorigenic potential was examined using a xenograft model in nude mice. Results SGPP2 and TFAP2A were upregulated in LUAD. High SGPP2 expression is closely associated with lymph node metastasis. Functional experiments demonstrated that SGPP2 promotes LUAD cell proliferation, migration, and epithelial-mesenchymal transition (EMT). Under physiological conditions, TFAP2A transcriptionally activates SGPP2 in LUAD cells, wherea