一种进化癌症表观遗传学方法揭示了不同哺乳动物鳞状细胞癌中超保守非编码元件的 DNA 超甲基化。
An Evolutionary Cancer Epigenetic Approach Revealed DNA Hypermethylation of Ultra-Conserved Non-Coding Elements in Squamous Cell Carcinoma of Different Mammalian Species.
机构信息
Functional MR Unit, Bellaria Hospital, Department of Biomedical and Neuromotor Sciences, University of Bologna, 40139 Bologna, Italy.
Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, Italy.
出版信息
Cells. 2020 Sep 13;9(9):2092. doi: 10.3390/cells9092092.
BACKGROUND
Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species.
METHODS
Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were collected as normal controls. Bisulfite next generation sequencing evaluated the DNA methylation level from seven UCNEs (uc.160, uc.283, uc.416, uc.339, uc.270, uc.299, and uc.328).
RESULTS
57/59 CpGs were significantly different according to the Kruskal-Wallis test ( < 0.05) comparing normal samples with SCC. A common DNA hypermethylation pattern was observed in SCCs from all the species evaluated in this study, with an increasing trend of hypermethylation starting from normal mucosa, through stomatitis to SCC.
CONCLUSIONS
Our findings indicate that UCNEs are hypermethylated in human SCC, and this behavior is also conserved among different species of mammals.
背景
超保守非编码元件（UCNEs）是在人类、哺乳动物、鸟类、爬行动物和鱼类之间具有>95%序列同一性的基因组序列。最近的研究结果报告了它们在癌症中的功能作用。本研究旨在评估不同哺乳动物鳞状细胞癌（SCC）中 UCNEs 的 DNA 甲基化修饰。
方法
共检测了 26 例人类、17 例猫、3 例狗、1 例马、1 例牛、1 例獾和 1 例豪猪的 50 例 SCC。收集了 36 例健康人类供体、7 只猫、5 只狗、5 匹马、2 头牛和 1 只獾的 14 例猫口腔炎和正常样本作为正常对照。亚硫酸氢盐下一代测序评估了来自七个 UCNEs（uc.160、uc.283、uc.416、uc.339、uc.270、uc.299 和 uc.328）的 DNA 甲基化水平。
结果
Kruskal-Wallis 检验比较正常样本与 SCC 时，57/59CpG 存在显著差异（<0.05）。在所评估的所有物种的 SCC 中均观察到常见的 DNA 高甲基化模式，从正常黏膜开始，通过口腔炎到 SCC，高甲基化趋势增加。
结论
我们的研究结果表明，UCNEs 在人类 SCC 中呈高甲基化状态，这种行为在不同的哺乳动物物种中也是保守的。
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