Bioinformatics analysis of dysregulated exosomal microRNAs derived from oral squamous cell carcinoma cells
Bioinformatics analysis of dysregulated exosomal microRNAs derived from oral squamous cell carcinoma cells
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DOI：
10.2334/josnusd.20-0662
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发表时间：
2021-03-01
影响因子：
1.9
通讯作者：
Tonogi, Morio
中科院分区：
文献类型：
--
作者：
Masaoka, Tadashi;Shinozuka, Keiji;Tonogi, Morio
目的：研究口腔鳞状细胞癌(OSCC)细胞系HSC-2、HSC-3、Ca9-22、HO-1-N1与正常角质形成细胞(HNOKs)外体miRNAs表达谱的差异。利用生物信息学方法对已鉴定的口腔鳞癌相关miRNAs及其潜在靶基因进行生物信息学分析，并用独创性路径分析(IPA)阐明已鉴定的口腔鳞癌细胞分泌的外体miRNAs的功能网络和基因本体论。结果：与HNOKs相比，OSCC细胞分泌的外体miRNAs中有8个上调，12个下调。IPA提出了这些异常miRNAs的潜在靶向mRNAs，通过遗传网络分析发现了6个显著的遗传网络。此外，还鉴定了4个关键的上游miRNAs-miR-125b-5p、miR-17-5p、miR-200b-3p和miR-23a-3p-。MIR-125b-5p是最重要网络的中心节点。基因本体论分析显示具有肿瘤相关功能的基因显著丰富，如肿瘤的分子机制、细胞周期、上皮-间充质转化的调控等。结论：这些结果全面揭示了口腔鳞癌中异常调节的外体miRNAs的功能，从而阐明了口腔鳞状细胞癌的发生发展。
Purpose: The present study aimed to identify dysregulated exosomal miRNAs associated with diagnostic and therapeutic biomarkers in oral squamous cell carcinoma (OSCC).Methods: 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.Results: 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.Conclusion: These results provide a comprehensive view of the functions of dysregulated exosomal miRNAs in OSCC, thus illuminating OSCC tumorigenesis and development.