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狗口腔黑色素瘤的转录组分析及其与人类黑色素瘤的致癌类比。

Transcriptome analysis of dog oral melanoma and its oncogenic analogy with human melanoma.

机构信息

Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890‑0065, Japan.

Joint Graduate School of Veterinary Medicine, Kagoshima University, Kagoshima 890‑0065, Japan.

出版信息

Oncol Rep. 2020 Jan;43(1):16-30. doi: 10.3892/or.2019.7391. Epub 2019 Oct 25.

DOI:10.3892/or.2019.7391
PMID:31661138
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6908934/
Abstract

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.

摘要

狗已被认为是人类黑色素瘤的一种极好的免疫活性模型,因为它们的肿瘤位置和临床及病理特征与人类黑色素瘤相同。然而,这两个物种之间的黑色素瘤转录组的差异尚未完全确定。鉴于癌基因在黑色素瘤发展中的作用,在本研究中,我们首先对犬口腔黑色素瘤的转录组进行了特征描述,然后将其与人类黑色素瘤的转录组进行了比较。通过 RNA-Seq 比较了 8 个犬口腔黑色素瘤样本和 3 个健康口腔组织的全转录组,并用 RT-qPCR 进行了验证。结果显示,有 2555 个注释的差异表达基因,以及 364 个新的差异表达基因。狗染色体 1 和 9 分别富集了下调和上调的基因。与 10 个显著的转录结合基序;NF-κB 和 ATF1 结合基序是最显著的,在上调的差异表达基因中鉴定出 4 个显著的未知基序。此外,研究发现犬口腔黑色素瘤与人类黑色素瘤共享 >80%的显著癌基因(上调基因),JAK-STAT 是两个物种之间最常见的显著通路。研究确定了一个在两种物种中都上调的黑色素瘤 429 基因特征,这些基因可能是治疗开发的良好候选基因。此外,本研究表明,就癌基因表达而言,人类黑色素瘤包含一个与犬口腔黑色素瘤具有相似性的癌基因群,这支持在人类应用之前,使用狗作为开发新疗法和实验试验的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/19a4033300eb/or-43-01-0016-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/e23708363d66/or-43-01-0016-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/c9b4aa92af5b/or-43-01-0016-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/3e9b3106ed6d/or-43-01-0016-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/19a4033300eb/or-43-01-0016-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/e23708363d66/or-43-01-0016-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/c9b4aa92af5b/or-43-01-0016-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/3e9b3106ed6d/or-43-01-0016-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f20/6908934/19a4033300eb/or-43-01-0016-g04.jpg

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