LIMA1 Is a Prognostic Senescence‐Inhibitory Gene in Head and Neck Squamous Carcinoma

ABSTRACT Background This study aimed to investigate potential cellular senescence inhibitory genes (CSIGs) and discover novel therapeutic targets in head and neck squamous cell carcinoma. Methods Dysregulated CSIGs were identified based on The Cancer Genome Atlas (TCGA) and the Human Aging Genomic Resources (HAGR) database. Prognostic value and immune infiltration were assessed through bioinformatic analysis. Cell proliferation was evaluated using CCK‐8, Edu assay, and colony formation assays in vitro. Western blotting and real‐time PCR were used to evaluate LIMA1 expression. Clinical validation of LIMA1 expression was performed in our validated cohort. Results In this study, differential analysis and functional enrichment analysis identified 26 differentially expressed senescence inhibitory genes. Among them, LIMA1 was found to be an independent prognostic marker and associated immune infiltration. Knockdown of LIMA1 inhibited HNSCC cell growth and increased the expression of senescence markers. Further experiments revealed that LIMA1 expression was partially regulated by the IL6/STAT3 signaling pathway. Immunohistochemistry further validated the clinical significance of LIMA1 expression and its association with IL6 and CD8 + T cells in our hospital's HNSCC tissues. Conclusion LIMA1 is a prognostic senescence‐inhibitory gene in HNSCC. The IL6/STAT3/LIMA1 axis represents a novel molecular mechanism underlying cellular senescence resistance in HNSCC.