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The aim of this study was to explore the regulatory role of epoxide hydrolase 3 (EPHX3) in head and neck squamous cell carcinoma (HNSCC) and to analyze its bioinformatic function, as well as, to screen and predict the miRNAs that can regulate EPHX3 expression in HNSCC. We examined the expression profile and prognostic potential of EPHX3 in TCGA and GTEX databases and performed functional enrichment analysis of EPHX3 using string database. Subsequently, we analyzed the regulatory role of miRNAs on EPHX3, including expression analysis, correlation analysis, and survival analysis. In addition, we also used TIMER to investigate the relationship among EPHX3 expression level, immune checkpoints, and immune infiltration in HNSCC. The results of data analysis after TGCA showed that EPHX3 is a key regulator of tumorigenesis in 13 cancers and can be used as a marker of poor prognosis in HNSCC patients. Bioinformatics analysis revealed that miR-4713-3p is a key miRNA of EPHX3 in HNSCC. Together, our findings indicate that EPHX3 exerts its anticancer effects by suppressing tumor immune checkpoint expression and immune cell infiltration. Overall, our data uncovered miRNA-mediated EPHX3 downregulation as a contributor to poor HNSCC prognosis and reduced tumor immune infiltration.

miRNA-Mediated Low Expression of EPHX3 Is Associated with Poor Prognosis and Tumor Immune Infiltration in Head and Neck Squamous Cell Carcinomas