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.
背景:头颈部鳞状细胞癌(HNSCC)是一种临床预后较差的常见恶性肿瘤。microRNA-7-5p(miR-7-5p)在不同组织环境中既被描述为肿瘤抑制因子,也被视为促癌miRNA,但其在HNSCC中的作用尚不明确。本研究旨在通过整合多源数据,阐明miR-7-5p在HNSCC中的临床意义及生物学功能。 方法:通过系统文献综述筛选分析人类头颈部组织miRNA表达的研究。对来自基因表达综合数据库(GEO)、ArrayExpress和癌症基因组图谱(TCGA)的个体患者数据进行荟萃分析,评估miR-7-5p在肿瘤与正常组织中的表达水平及其与临床参数和预后的关联。采用生物信息学分析预测miR-7-5p靶基因,筛选枢纽基因并进行基因本体富集分析。通过组织样本、HNSCC细胞系及口腔癌体外模型的microRNA原位杂交(miRNA ISH)和实时定量PCR(RT-qPCR)验证miR-7-5p表达模式。 结果:与正常组织相比,miR-7-5p在肿瘤组织中显著上调,且与较大肿瘤体积、HPV阴性状态、较差的疾病特异性生存期及较短的无进展生存期相关。生物信息学分析显示miR-7-5p靶基因富集于细胞生长、存活和肿瘤发生相关通路。尽管临床前模型中外源性miR-7-5p具有抗癌作用的证据,但观察到的肿瘤内源性上调现象提示,miR-7-5p的表达可能代表肿瘤发生过程中的代偿性或应激响应机制,而非作为主要致癌驱动因子。 结论:本研究为miR-7-5p在HNSCC中的复杂作用提供了新见解,支持其作为生物标志物和治疗靶点的双重潜力。理解miR-7-5p在特定环境下的功能对于开发基于RNA的HNSCC治疗方法至关重要。