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肺癌细胞中的差异化超级增强子。

Differentiated super-enhancers in lung cancer cells.

机构信息

Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.

出版信息

Sci China Life Sci. 2019 Sep;62(9):1218-1228. doi: 10.1007/s11427-018-9319-4. Epub 2019 Jan 9.

Abstract

Super-enhancers (SEs) are regulatory elements with enriched accumulation of key transcription factors. Few studies were done investigating SEs in lung cancers. Here we analyzed epigenetic profiling data to identify SEs in lung cancer cell lines. Enhancers were classified as SEs and typical enhancers (TEs). Most of the TEs were overlapped between normal cell and cancer cells. A great portion of SEs were differentiated comparing these cells. Analysis of GO terms associated with SEs revealed SE remodeling (lost on some sites while gain on others) between normal and lung cancer cells. By comparing the average number of SEs in each GO term in cancer cells with the number in control cells, surprisingly, no GO terms with significantly increased SE number in cancer condition were observed. On the contrary, in aspects such as "cell-cell adhesion", "receptor activity" and "negative regulation of canonical Wnt signaling pathway", the related SEs were significantly reduced in cancer cells. These findings suggest that in lung cancer, cells may not gain decisive gene expression in the related aspect, instead, they may have lost control of the fateful genes. Taken together, our work with the usability of omics data identified SEs in lung cancer cells and further showed cancer-specific features of SE-related terms.

摘要

超级增强子(SEs)是富含关键转录因子积累的调控元件。很少有研究调查肺癌中的 SEs。在这里,我们分析了表观遗传谱数据,以鉴定肺癌细胞系中的 SEs。增强子被分类为 SEs 和典型增强子(TEs)。大多数 TEs 在正常细胞和癌细胞之间重叠。比较这些细胞时,很大一部分 SEs 存在差异。与 SEs 相关的 GO 术语分析表明,SE 在正常细胞和肺癌细胞之间发生了重塑(在一些位点丢失,而在另一些位点获得)。通过比较癌症细胞中每个 GO 术语中 SE 的平均数量与对照细胞中的数量,令人惊讶的是,在癌症条件下,没有观察到 SE 数量显著增加的 GO 术语。相反,在“细胞-细胞粘附”、“受体活性”和“经典 Wnt 信号通路的负调控”等方面,相关 SEs 在癌细胞中显著减少。这些发现表明,在肺癌中,细胞在相关方面可能不会获得决定性的基因表达,而是可能失去对关键基因的控制。总之,我们利用组学数据的可用性,鉴定了肺癌细胞中的 SEs,并进一步显示了与 SE 相关术语的癌症特异性特征。

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