Fatty Acid‐Binding Protein 5 Potentially Regulates the Proliferation and Metastasis of Uveal Melanoma Cells Through the PI3K/AKT/mTOR Signaling Pathway

Abstract

ABSTRACT Background Uveal melanoma (UVM) is an aggressive intraocular tumor with limited effective treatments for metastatic disease. This study explored the pathways through which fatty acid‐binding protein 5 (FABP5) promoted UVM progression. Methods Single‐cell RNA sequencing datasets were preprocessed by the Seurat package, and prognostic genes were screened using the survival package. A prognostic model was constructed via LASSO Cox regression, followed by Kaplan–Meier (KM) survival analysis. To characterize the tumor immune microenvironment, we evaluated immune cell infiltration using ssGSEA, ESTIMATE, and CIBERSORT algorithms, while GSEA was applied to identify enriched pathways. Additionally, immunotherapy response was predicted by TIDE, and tumor mutation burden (TMB) was calculated using Maftools. For in vivo validation, a nude mouse xenograft model was established, and Western blotting was performed on tumor tissues harvested from the xenograft assay. Results SPON2, MATK, and FABP5 were identified as hub genes in UVM and used to construct a prognostic model with a high AUC. Immune infiltration analysis revealed that high‐risk patients exhibited features of immune evasion. Enrichment analysis further revealed that cytotoxic T‐cell‐related genes (MATK and FABP5) were enriched in the PI3K/AKT/mTOR pathway. FABP5 was overexpressed in UVM cells, whereas FABP5 silencing suppressed cell viability, proliferation, migration, and invasion, reduced MMP2 and MMP9 levels, promoted apoptosis, downregulated PI3K/AKT/mTOR pathway‐related molecules, and upregulated apoptosis‐related proteins. Notably, these effects could be reversed by the PI3K agonist 740Y‐P. Conclusion FABP5 promoted UVM cell proliferation and migration through the PI3K/AKT/mTOR pathway. Though the immune‐infiltration analysis was hypothesis‐generating, it may help identify patients likely to benefit from immunotherapy.