TRIM32 drives head and neck squamous cell carcinoma progression via TP53 suppression and lysosomal/autophagy dysregulation

Background: The TRIM32 has been implicated in tumorigenesis across various cancers; however, its functional significance in head and neck squamous cell carcinoma (HNSCC) requires systematic investigation. This study sought to explore the expression and biological function of TRIM32 in HNSCC tissues to identify new targets or biomarkers for HNSCC diagnosis and treatment.

Methods: HNSCC samples were extracted for TRIM32 expression profiling, with subsequent integration of clinical samples for validation. Gene Set Enrichment Analysis (GSEA) was performed using the c2.cp.kegg.v7.4.symbols.gmt gene set. Immune cell infiltration was evaluated using the ESTIMATE algorithm. Following TRIM32 knockdown via small interfering RNA (siRNA) in HNSCC cell lines (HSC-3, FADU), proliferation and invasion capacities were assessed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Western blotting was conducted to analyse protein expression within the TRIM32-p53-LAMP1/2-LC3B pathway.

Results: Integrated bioinformatics analysis and clinical sample validation revealed significantly elevated TRIM32 expression in HNSCC, correlating with poor patient prognosis. GSEA demonstrated significant enrichment of autophagy and p53 signalling pathways within the TRIM32 high-expression group. In vitro experiments confirmed that TRIM32 silencing suppressed proliferation and invasion capacities in HSC-3 and FADU cell lines. Western blotting further delineated that TRIM32 regulates autophagic flux through the TRIM32-p53-LAMP1/2-LC3B axis. The ESTIMATE algorithm indicated a significant association between TRIM32 expression and immune cell infiltration, suggesting a potential role in remodelling the tumour immune microenvironment.

Conclusions: TRIM32 expression is significantly elevated in HNSCC, indicating its potential as an adverse prognostic marker. Experimental evidence demonstrates that TRIM32 facilitates cellular proliferation and migration, significantly influences lysosomal function and autophagy processes within HNSCC cells, and is verified to negatively regulate tumour protein 53 (TP53). These mechanisms contribute to the aggressive behaviour of HNSCC.