117742The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China.
Guangxi Tumor Radiation Therapy Clinical Medical Research Center, Nanning, Guangxi, P.R. China.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221081245. doi: 10.1177/15330338221081245.
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. 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. MiR-21-5p was significantly overexpressed in HNSCC compared to healthy tissues ( < .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 ( < .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. 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.
头颈部鳞状细胞癌(HNSCC)是全球第六种最常见的恶性肿瘤。已有研究报道,microRNA-21-5p(miR-21-5p)的过表达与 HNSCC 的发生发展有关。然而,miR-21-5p 在 HNSCC 中的作用仍未完全阐明。本研究旨在探讨 miR-21-5p 在 HNSCC 中的潜在分子机制。采用 RT-qPCR 检测 HNSCC 患者组织样本中 miR-21-5p 的差异表达水平。基于从基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和已发表文章中收集的 miRNA 表达数据进行荟萃分析,评估 miR-21-5p 在 HNSCC 中的表达情况。通过基因本体富集和靶基因预测分析研究 miR-21-5p 的生物学功能。此外,采用 RT-qPCR 和免疫组织化学(IHC)检测验证靶基因的表达。最后,进行 Kaplan-Meier 生存分析评估潜在 miR-21-5p 靶基因的预后价值。结果显示,miR-21-5p 在 HNSCC 中显著高表达,与健康组织相比差异有统计学意义(<0.05),且具有较高的预测能力,汇总受试者工作特征曲线下面积为 0.90。同时,miR-21-5p 的表达与 HNSCC 的肿瘤分期、T 分期和吸烟史显著相关(<0.05)。通过分析整合共获得 71 个下调基因,包括与 HNSCC 相关和 miR-21-p5 相关的基因。预测到的两个靶基因(ADH7、RDH12)在 HNSCC 中下调,且与 miR-21-5p 呈显著负相关。IHC 和 RT-qPCR 结果显示,ADH7 和 RDH12 在 HNSCC 样本中的表达明显低于对照组。ADH7 高表达与 HNSCC 患者的DFS 较好相关。提示 miR-21-5p 可能靶向 ADH7、RDH12 并参与视黄醇代谢的调控,这可能影响 HNSCC 的预后。ADH7 高表达可能预示 HNSCC 患者预后较好。