# Systematic Review and Meta-Analysis of microRNA-7-5p Expression and Biological Significance in Head and Neck Squamous Cell Carcinoma

## TL;DR

This study explores how microRNA-7-5p behaves in head and neck cancer, finding it is linked to worse outcomes but also has potential as a treatment target.

## Contribution

The study clarifies the dual role of miR-7-5p in head and neck cancer as both a biomarker and a potential therapeutic target.

## Key findings

- miR-7-5p is upregulated in tumors and associated with poor clinical outcomes like larger tumor size and shorter survival.
- Bioinformatics analysis shows miR-7-5p targets genes involved in cancer-related pathways.
- Endogenous miR-7-5p may act as a compensatory mechanism rather than a direct driver of cancer.

## Abstract

This study addresses the complex role of miR-7-5p in head and neck cancer, a disease with limited treatment options and poor survival rates. By integrating patient data, bioinformatics predictions, and laboratory experiments, our study demonstrated that miR-7-5p is frequently upregulated in tumours and linked to worse clinical outcomes. Yet, overwhelming evidence demonstrates the anti-cancer functions of synthetic miR-7-5p mimics. This comprehensive approach enhances our understanding of the role of miR-7-5p in cancer biology and provides a foundation for developing RNA-based therapies in head and neck cancer.

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC.