Author Identifier (ORCID)
Andrew J. Woo: https://orcid.org/0000-0003-1198-6373
Abstract
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.
Document Type
Journal Article
Date of Publication
10-1-2025
Volume
17
Issue
19
Publication Title
Cancers
Publisher
MDPI
School
School of Medical and Health Sciences
RAS ID
84400
Funders
Australian Government Research Training Program Scholarship / Kirkbride Melanoma Centre / National Health and Medical Research Council / Garnett Passe and Rodney Williams Memorial Foundation (11407) / Phenomics Australia
Grant Number
NHMRC Number : 2029660A
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Brown, R. a. M., Phillips, M., Woo, A. J., Kujan, O., Flukes, S., Winteringham, L. N., Dymond, L. C., Wheeler, F., Pollock, B., Beveridge, D. J., Denisenko, E., & Leedman, P. J. (2025). Systematic review and meta-analysis of microRNA-7-5p expression and biological significance in head and neck squamous cell carcinoma. Cancers, 17(19), 3232. https://doi.org/10.3390/cancers17193232