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

## TL;DR

This paper reviews how the long non-coding RNA NEAT1 contributes to head and neck cancer progression and its potential as a biomarker and therapeutic target.

## Contribution

The paper provides a comprehensive review of NEAT1's molecular mechanisms and clinical implications in HNSCC.

## Key findings

- NEAT1 promotes HNSCC progression by acting as a ceRNA for miRNAs like miR-125b-5p and miR-34a-5p.
- High NEAT1 expression correlates with metastasis and poor survival in HNSCC patients.
- Nanoparticle-based gene silencing offers a potential therapeutic strategy to target NEAT1.

## Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with limited treatment options and poor survival rates. This review focuses on a specific long non-coding RNA NEAT1 (LncRNA NEAT1), which is often found at high levels in HNSCC. We summarize how LncRNA NEAT1 acts as a key driver of cancer progression—promoting tumor growth, spread, and resistance to therapy—by interacting with multiple microRNAs and activating several cancer-related signaling pathways. Clinically, high LncRNA NEAT1 expression is linked to advanced disease stage, metastasis, and worse patient outcomes, indicating its potential as a diagnostic and prognostic biomarker. Although directly targeting LncRNA NEAT1 therapeutically remains challenging, emerging approaches such as nanoparticle-based gene silencing offer promising strategies. Understanding the role of LncRNA NEAT1 may help advance precision medicine and improve future treatments for HNSCC patients.

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.