TRIML2 promotes malignant progression of head and neck squamous cell carcinoma via canonical Wnt signaling and tumor immune escape

Background The roles and underlying mechanisms of tripartite motif family like 2 (TRIML2) in tumors, including head and neck squamous cell carcinoma (HNSC), remain poorly characterized. This study aimed to comprehensively characterize the significance of TRIML2 in HNSC using multi-omics analyses and experimental validation. Methods Differentially expressed genes in HNSC were screened from TCGA and GEO datasets, and TRIML2 was identified as a hub gene for further investigation. Its expression patterns, diagnostic and prognostic value, associations with clinicopathological features, drug sensitivity, and immune infiltration were systematically analyzed. Gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) network analysis were performed to explore TRIML2-related signaling pathways. The biological function and molecular mechanisms of TRIML2 were further validated through in vitro and in vivo experiments. Results TRIML2 was significantly upregulated in HNSC, and correlated with worse overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS). High TRIML2 expression was associated with advanced tumor stage, distant metastasis, increased infiltration of immunosuppressive cells, elevated expression of immunosuppressive molecules, and activation of multiple oncogenic pathways. Silencing TRIML2 inhibited cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), canonical Wnt pathway activity, immunosuppressive molecule expression and tumor growth in vitro and in vivo, whereas TRIML2 overexpression produced the opposite effects. Conclusions TRIML2 promotes malignant progression of HNSC by activating the canonical Wnt pathway and facilitating tumor immune escape. TRIML2 represents a promising biomarker for diagnosis, immunotherapy, and prognosis in HNSC.