Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanoma
Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanoma
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DOI：
10.3892/or.2019.7391
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发表时间：
2019-10
期刊：
影响因子：
4.2
通讯作者：
Md Mahfuzur Rahman;Y. Lai;A. Husna;Hui-Wen Chen;Yuiko Tanaka;H. Kawaguchi;H. Hatai;N. Miyoshi;T. Nakagawa;R. Fukushima;N. Miura
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文献类型：
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作者：
Md Mahfuzur Rahman;Y. Lai;A. Husna;Hui-Wen Chen;Yuiko Tanaka;H. Kawaguchi;H. Hatai;N. Miyoshi;T. Nakagawa;R. Fukushima;N. Miura
狗与人类黑色素瘤具有相同的肿瘤部位和共同的临床病理特征，被认为是治疗人类黑色素瘤的良好免疫模型。然而，这两个物种之间的黑色素瘤转录组的差异还没有完全确定。考虑到癌基因在黑色素瘤发生发展中的作用，在本研究中，我们首先描述了犬口腔黑色素瘤的转录组，然后将转录组与人类黑色素瘤的转录组进行了比较。对8例犬口腔黑色素瘤组织和3例正常口腔组织的总转录组进行了RNA-Seq分析和RT-qPCR验证。结果发现2555个注释差异表达基因，以及364个新的差异表达基因。狗的1号和9号染色体分别富含下调和上调的基因。与10个重要的转录结合基序一起，在上调的差异表达基因中，最重要的是NF-κB和ATF1结合基序，还有4个重要的未知基序。此外，还发现犬口腔黑色素瘤与人类黑色素瘤有80%的显著癌基因(上调基因)相同，JAK-STAT是物种间最常见的显著途径。结果确定了黑色素瘤中的429基因特征，该基因在两个物种中都上调；这些基因可能是很好的治疗开发候选基因。此外，本研究还表明，在癌基因表达方面，人类黑色素瘤包含一个与狗口腔黑色素瘤相似的癌基因群，这支持在人类应用之前将狗作为开发新疗法和实验试验的模型。
Dogs have been considered as an excellent immunocompetent model for human melanoma due to the same tumor location and the common clinical and pathological features with human melanoma. However, the differences in the melanoma transcriptome between the two species have not been yet fully determined. Considering the role of oncogenes in melanoma development, in this study, we first characterized the transcriptome in canine oral melanoma and then compared the transcriptome with that of human melanoma. The global transcriptome from 8 canine oral melanoma samples and 3 healthy oral tissues were compared by RNA-Seq followed by RT-qPCR validation. The results revealed 2,555 annotated differentially expressed genes, as well as 364 novel differentially expressed genes. Dog chromosomes 1 and 9 were enriched with downregulated and upregulated genes, respectively. Along with 10 significant transcription site binding motifs; the NF-κB and ATF1 binding motifs were the most significant and 4 significant unknown motifs were indentified among the upregulated differentially expressed genes. Moreover, it was found that canine oral melanoma shared >80% significant oncogenes (upregulated genes) with human melanoma, and JAK-STAT was the most common significant pathway between the species. The results identified a 429 gene signature in melanoma, which was up-regulated in both species; these genes may be good candidates for therapeutic development. Furthermore, this study demonstrates that as regards oncogene expression, human melanoma contains an oncogene group that bears similarities with dog oral melanoma, which supports the use of dogs as a model for the development of novel therapeutics and experimental trials before human application.