Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer
Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer
复制标题
通过表观遗传修饰上调 DLEU1 表达可促进人类癌症的肿瘤发生。
DOI：
10.1002/jcp.28364
复制
发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Xu, Shouping
中科院分区：
文献类型：
--
作者：
Pang, Boran;Sui, Shiyao;Xu, Shouping
DLEU1在人类癌症中的功能在很大程度上是未知的。癌症基因组图谱数据被应用于识别肿瘤组织和正常组织之间的差异基因景观，这被我们的队列数据和包括33种癌症类型和11，060名患者的泛癌症数据进一步验证。接下来，选择DLEU1来验证新的发现，结果表明它在体外和体内促进肿瘤发生。机制上，DLEU1通过表观遗传学增加H3K27ac富集到SRP4基因座来促进SRP4表达。此外，表观遗传修饰通过降低DNA甲基化和增加其基因座中的H3K27ac和H3K4me3组蛋白修饰导致DLEU1表达上调。最后，DLEU1的高表达不仅在特定癌症类型患者中，而且在泛癌症队列中的患者中与更差的预后相关。总之，这项工作拓宽了已知的长非编码RNA在人类癌症中的功能，并为它们在肿瘤发生中的作用提供了新的见解。
The function of DLEU1 in human cancer is largely unknown. The Cancer Genome Atlas data were applied to identify the landscape of differential genes between tumor tissues and normal tissues, which was further validated by our cohort data and pan-cancer data including 33 cancer types with 11,060 patients. Next, DLEU1 was selected to validate the novel finding and result showed that it promoted tumorigenesis in vitro and in vivo. Mechanistically, DLEU1 promotes SRP4 expression via increasing H3K27ac enrichment to SRP4 locus epigenetically. Moreover, epigenetic modification leads to upregulation of DLEU1 expression via decreased DNA methylation and increased H3K27ac and H3K4me3 histone modification in its locus. Finally, high expression of DLEU1 correlates with worse prognosis not only in specific cancer type patients but also in patients in the pan-cancer cohort. In summary, the work broadens the function landscape of known long noncoding RNAs in human cancer and provides novel insights into their roles in tumorigenesis.