犬口腔黑色素瘤中长链非编码 RNA 谱的全基因组分析。

Genome-Wide Analysis of Long Non-Coding RNA Profiles in Canine Oral Melanomas.

机构信息

University of Rennes, CNRS, IGDR-UMR 6290, F-35000 Rennes, France.

Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003 Barcelona, Spain.

出版信息

Genes (Basel). 2019 Jun 23;10(6):477. doi: 10.3390/genes10060477.

Abstract

Mucosal melanomas (MM) are rare aggressive cancers in humans, and one of the most common forms of oral cancers in dogs. Similar biological and histological features are shared between MM in both species, making dogs a powerful model for comparative oncology studies of melanomas. Although exome sequencing recently identified recurrent coding mutations in canine MM, little is known about changes in non-coding gene expression, and more particularly, in canine long non-coding RNAs (lncRNAs), which are commonly dysregulated in human cancers. Here, we sampled a large cohort ( = 52) of canine normal/tumor oral MM from three predisposed breeds (poodles, Labrador retrievers, and golden retrievers), and used deep transcriptome sequencing to identify more than 400 differentially expressed (DE) lncRNAs. We further prioritized candidate lncRNAs by comparative genomic analysis to pinpoint 26 dog-human conserved DE lncRNAs, including , , and lncRNAs. Using unsupervised co-expression network analysis with coding genes, we inferred the potential functions of the DE lncRNAs, suggesting associations with cancer-related genes, cell cycle, and carbohydrate metabolism Gene Ontology (GO) terms. Finally, we exploited our multi-breed design to identify DE lncRNAs within breeds. This study provides a unique transcriptomic resource for studying oral melanoma in dogs, and highlights lncRNAs that may potentially be diagnostic or therapeutic targets for human and veterinary medicine.

摘要

黏膜黑色素瘤(MM)是人类罕见的侵袭性癌症,也是犬类最常见的口腔癌之一。这两种物种的 MM 具有相似的生物学和组织学特征,这使得犬类成为黑色素瘤比较肿瘤学研究的有力模型。尽管外显子组测序最近确定了犬类 MM 中的反复出现的编码突变,但对于非编码基因表达的变化,特别是犬类长非编码 RNA(lncRNA)的变化知之甚少,lncRNA 在人类癌症中通常失调。在这里,我们从三个易患品种(贵宾犬、拉布拉多猎犬和金毛猎犬)中采样了大量的犬类正常/肿瘤口腔 MM (n = 52),并使用深度转录组测序鉴定了超过 400 个差异表达(DE)的 lncRNA。我们通过比较基因组分析进一步对候选 lncRNA 进行了优先级排序,以确定 26 个犬-人保守的 DE lncRNA,包括 、 和 lncRNA。通过与编码基因的无监督共表达网络分析,我们推断了 DE lncRNA 的潜在功能,表明与癌症相关基因、细胞周期和碳水化合物代谢基因本体论(GO)术语有关。最后,我们利用多品种设计来鉴定品种内的 DE lncRNA。这项研究为研究犬类口腔黑色素瘤提供了独特的转录组资源,并强调了可能成为人类和兽医医学诊断或治疗靶点的 lncRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed81/6628375/3c7ff24eb02c/genes-10-00477-g001.jpg

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