Transposable elements drive widespread expression of oncogenes in human cancers
Transposable elements drive widespread expression of oncogenes in human cancers
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DOI：
10.1038/s41588-019-0373-3
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发表时间：
2019-04-01
期刊：
影响因子：
30.8
通讯作者：
Wang, Ting
中科院分区：
文献类型：
--
作者：
Jang, Hyo Sik;Shah, Nakul M.;Wang, Ting
转座因子（Transposable elements，TE）是调控序列的丰富遗传资源（1-3）。TE内的隐藏调节元件可以在癌症中表观遗传地重新激活，以在称为肿瘤外适应的过程中影响肿瘤发生（4）。然而，TE肿瘤外适应事件在不同癌症类型中的患病率和影响特征很差。在这里，我们分析了来自15种癌症类型的7，769个肿瘤和625个正常数据集，在3，864个肿瘤中鉴定了涉及106个癌基因的129个TE隐蔽启动子激活事件。此外，我们询问了TEMJb-LIN 28 B候选者：TE的遗传缺失消除了癌基因表达，而动态DNA甲基化调节了启动子活性，说明了TE对癌基因激活的必要性和充分性。总的来说，我们的研究结果表征了TE肿瘤外适应的全球概况，并强调这种普遍现象是混杂癌基因激活和最终肿瘤发生的重要机制。
Transposable elements (TEs) are an abundant and rich genetic resource of regulatory sequences(1-3). Cryptic regulatory elements within TEs can be epigenetically reactivated in cancer to influence oncogenesis in a process termed onco-exaptation(4). However, the prevalence and impact of TE onco-exaptation events across cancer types are poorly characterized. Here, we analyzed 7,769 tumors and 625 normal datasets from 15 cancer types, identifying 129 TE cryptic promoter-activation events involving 106 oncogenes across 3,864 tumors. Furthermore, we interrogated the AluJb-LIN28B candidate: the genetic deletion of the TE eliminated oncogene expression, while dynamic DNA methylation modulated promoter activity, illustrating the necessity and sufficiency of a TE for oncogene activation. Collectively, our results characterize the global profile of TE onco-exaptation and highlight this prevalent phenomenon as an important mechanism for promiscuous oncogene activation and ultimately tumorigenesis.