The Oncogenic Role of Long Non-Coding RNA NEAT1 in Head and Neck Squamous Cell Carcinoma: From Molecular Mechanisms to Clinical Implications

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with poor patient outcomes. The long non-coding RNA NEAT1 (lncRNA NEAT1) has emerged as a critical driver of HNSCC pathogenesis. This review synthesizes current knowledge on lncRNA NEAT1’s aberrant expression, molecular mechanisms, and functional roles in HNSCC. LncRNA NEAT1 is significantly upregulated in tumors and promotes progression by acting as a competing endogenous RNA (ceRNA) for multiple miRNAs, such as miR-125b-5p, miR-204, and miR-34a-5p, thereby regulating downstream targets including SLC1A5, ZEB1, and components of the Wnt/β-catenin pathway. These interactions drive key oncogenic processes, including proliferation, metastasis, epithelial–mesenchymal transition, therapy resistance, and cell death inhibition. Clinically, high lncRNA NEAT1 expression correlates with advanced T stage, lymph node metastasis, and reduced survival, underscoring its potential as a diagnostic and prognostic biomarker. Therapeutically, emerging approaches such as nanoparticle-mediated delivery of siRNA/shRNA offer a promising strategy to target lncRNA NEAT1, potentially synergizing with existing immunotherapies. Although clinical translation remains challenging, lncRNA NEAT1 represents a highly promising biological target for future precision oncology in HNSCC.