Division of Oral Structural and Functional Biology, Nihon University Graduate School of Dentistry.
Department of Oral and Maxillofacial Surgery, Nihon University School of Dentistry.
J Oral Sci. 2021 Mar 31;63(2):174-178. doi: 10.2334/josnusd.20-0662. Epub 2021 Mar 18.
The present study aimed to identify dysregulated exosomal miRNAs associated with diagnostic and therapeutic biomarkers in oral squamous cell carcinoma (OSCC).
Microarray analysis was used to compare expression profiles of exosomal miRNAs in the OSCC-derived cell lines HSC-2, HSC-3, Ca9-22, and HO-1-N1 with those in human normal keratinocytes (HNOKs). The identified OSCC-related miRNAs and their potential target genes were analyzed with bioinformatic analyses, and the data were subjected to Ingenuity Pathway Analysis (IPA) to clarify functional networks and gene ontologies of the identified exosomal miRNAs secreted by OSCC cells.
Comparison with HNOKs detected 8 upregulated and 12 downregulated miRNAs in OSCC-secreted exosomes. The potential target mRNAs of these dysregulated miRNAs were suggested by IPA, and 6 significant genetic networks were indicated by genetic network analysis. Furthermore, 4 crucial upstream miRNAs-miR-125b-5p, miR-17-5p, miR-200b-3p, and miR-23a-3p-were identified. miR-125b-5p was a central node in the most significant network. Gene ontology analysis showed significant enrichment of genes with cancer-related functions, such as molecular mechanisms of cancer, cell cycle, and regulation of the epithelial-mesenchymal transition.
These results provide a comprehensive view of the functions of dysregulated exosomal miRNAs in OSCC, thus illuminating OSCC tumorigenesis and development.
本研究旨在鉴定与口腔鳞状细胞癌(OSCC)诊断和治疗生物标志物相关的失调外泌体 miRNA。
使用微阵列分析比较 OSCC 衍生细胞系 HSC-2、HSC-3、Ca9-22 和 HO-1-N1 中的外泌体 miRNA 表达谱与正常人角质形成细胞(HNOK)中的表达谱。利用生物信息学分析鉴定 OSCC 相关 miRNA 及其潜在靶基因,并对 IPA 进行数据分析,以阐明 OSCC 细胞分泌的外泌体 miRNA 的功能网络和基因本体论。
与 HNOK 相比,在 OSCC 分泌的外泌体中检测到 8 个上调和 12 个下调的 miRNA。IPA 提示这些失调 miRNA 的潜在靶 mRNAs,遗传网络分析提示 6 个显著的遗传网络。此外,还鉴定出 4 个关键的上游 miRNA-miR-125b-5p、miR-17-5p、miR-200b-3p 和 miR-23a-3p。miR-125b-5p 是最显著网络中的中心节点。基因本体论分析显示,与癌症相关功能的基因显著富集,如癌症的分子机制、细胞周期和上皮-间充质转化的调控。
这些结果提供了失调外泌体 miRNA 在 OSCC 中的功能的全面视图,从而阐明了 OSCC 的肿瘤发生和发展。