Investigation of miR-21-5p Key Target Genes and Pathways in Head and Neck Squamous Cell Carcinoma Based on TCGA Database and Bioinformatics Analysis.

Aim: Head and neck squamous cell carcinoma (HNSCC) is the sixth most commonly diagnosed malignancy worldwide. Overexpressed of microRNA-21-5p (miR-21-5p) has been reported to be involved in the development of HNSCC. However, the role of miR-21-5p in HNSCC is still not fully elucidated. The purpose of this study was to explore the underlying molecular mechanisms of miR-21-5p in HNSCC. Methods: RT-qPCR was used to determine the differential expression levels of miR-21-5p in tissue samples of HNSCC patients. Meta-analysis was performed based on miRNA expression data collected from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA), and published articles to evaluate the expression of miR-21-5p in HNSCC. We investigated the biological function of miR-21-5P by gene ontology enrichment and target prediction analysis. Furthermore, RT-qPCR and IHC were conducted to verify the expression of target genes. Finally, Kaplan-Meier survival analysis was performed to assessed the prognostic value of the putative miR-21-5p target genes. Results: MiR-21-5p was significantly overexpressed in HNSCC compared to healthy tissues (P < .05) and showed potent predictive power with a summary receiver operating characteristic of 0.90. Meanwhile, the expression of miR-21-5p was significantly correlated with tumor stage, T stage and smoking in HNSCC (P < .05). A total of 71 down-regulated genes, both HNSCC-related and miR-21-p5-related, were obtained from the analytical integration. Two predicted genes (ADH7, RDH12) were down-regulated in HNSCC, and significantly negatively correlated with miR-21-5p. IHC and RT-qPCR demonstrated that the expression of ADH7 and RDH12 in HNSCC samples was significantly lower than control. And high expression of ADH7 was associated with better DFS of HNSCC patients. Conclusions: miR-21-5p may target at ADH7, RDH12 and participate in regulation of retinol metabolism, which might affect the prognosis of HNSCC. High expression of ADH7 may indicate better prognosis in HNSCC patients.

Expression and Possible Molecular Mechanisms of microRNA-205-5p in Patients With Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide, with high incidence and poor survival rates. Increased expression of microRNA-205-5p (miR-205-5p) may influence the outcomes of HNSCC, but the identities of miR-205-5p target genes and the potential signaling pathways related to HNSCC remain unclear. RT-qPCR was used to detect the expression levels of miR-205-5p in the plasma of patients with HNSCC. We also performed a meta-analysis using data from relevant literature, and the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases to evaluate the expression level of miR-205-5p in HNSCC. Next, we predicted the potential miR-205-5p target genes in HNSCC. We also used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for enrichment analyses adapted to investigate the dynamics and possible mechanisms of miR-205-5p in HNSCC. Lastly, we predicted the potential miR-205-5p target genes by evaluating their expression level and using Spearman analysis. Expression of miR-205-5p was higher in HNSCC tissues compared to normal unafflicted tissue samples (P < 0.05), and the corresponding summary receiver operating characteristic (sROC) was 0.82.The pooled sensitivity, specificity, PLR, NLR, and DOR values were 0.78 (95% CI: 0.75-0.81), 0.67 (95% CI: 0.60-0.73), 2.34 (95% CI: 1.45-3.76), 0.34 (95% CI: 0.19-0.60), and 8.16 (95% CI: 4.01-16.64), respectively. Based on GO and KEGG analyses, we found that miR-205-5p was correlated with the progression of HNSCC through association with signaling pathways, including the drug metabolism-cytochrome P450 pathway. Analysis of the target genes revealed that flavin-containing monooxygenase isoform 2 (FMO2) and alcohol dehydrogenase 1B (ADH1B) may be important targets of miR-205-5p. In summary, miR-205-5p may have a significant role in the prognosis of HNSCC and may serve as a potential biomarker in HNSCC.