Qian Mingming, Wang Wenzhu, Zhang Yana, Zhao Yi, Quan Huige, Chen Yuting, Dai Xinyue, Guo Zhiyun
School of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Precis Clin Med. 2021 Aug 2;4(3):204-208. doi: 10.1093/pcmedi/pbab019. eCollection 2021 Sep.
Enhancers are often mutated and dysregulated in various diseases such as cancer. By integrating the function annotation of the mammalian genome (FANTOM) enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas (TCGA) of 13 cancers and their corresponding -cancerous tissues, we systematically identified a total of 4702 significantly differentially expressed (DE) enhancers. Furthermore, a total of 1036 DE genes regulated by DE enhancers were identified. It was found that in these 13 cancers, most (61.13%) enhancers were ubiquitously expressed, whereas DE enhancers were more likely to be tissue-specific expressed, and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways. Finally, it was manifested that 74 single nucleotide polymorphisms (SNPs) were located in 37 DE enhancers, and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors, which were shown to be highly correlated with tumorigenesis and development.
增强子在多种疾病（如癌症）中常常发生突变并失调。通过整合哺乳动物基因组功能注释（FANTOM）增强子表达谱以及来自13种癌症及其相应癌旁组织的癌症基因组图谱（TCGA）的RNA测序数据，我们系统地鉴定出总共4702个显著差异表达（DE）增强子。此外，还鉴定出了总共1036个由DE增强子调控的DE基因。研究发现，在这13种癌症中，大多数（61.13%）增强子是普遍表达的，而DE增强子更可能是组织特异性表达的，并且由DE增强子调控的DE基因在癌症相关通路中显著富集。最后，结果表明74个单核苷酸多态性（SNP）位于37个DE增强子中，这些SNP影响了758个转录因子的功能性转录因子结合位点的增减，这些转录因子与肿瘤发生和发展高度相关。
