Identification of epigenetic interactions between miRNA and DNA methylation associated with gene expression as potential prognostic markers in bladder cancer.
Identification of epigenetic interactions between miRNA and DNA methylation associated with gene expression as potential prognostic markers in bladder cancer.
复制标题
DOI：
10.1186/s12920-017-0269-y
复制
发表时间：
2017-05-24
影响因子：
2.7
通讯作者：
Kim D
中科院分区：
文献类型：
--
作者：
Shivakumar M;Lee Y;Bang L;Garg T;Sohn KA;Kim D
癌症的基本挑战之一是检测癌症进展过程中基因表达变化的调节因子。通过关键癌症相关基因的转录沉默，表观遗传变化如DNA甲基化在癌症中起着至关重要的作用。此外，表观基因组的另一个主要组成部分miRNA也是转录后水平的调节因子，调节转录组的变化。然而，DNA甲基化和miRNA作为转录组学变化的表观遗传调节因子之间的协同相互作用的机制作用及其与临床结果如存活率的关联在癌症中仍然在很大程度上未被探索。在这项研究中，我们提出了一个整合的框架，以确定甲基化和与转录组变化相关的miRNA之间的表观遗传相互作用。为了测试所提出的框架的效用，本研究分析了来自癌症基因组图谱（TCGA）的膀胱癌数据集，包括DNA甲基化、miRNA表达和基因表达数据。首先，我们发现了120个与两个表观基因组成分之间的相互作用相关的基因。然后，发现miRNA和甲基化之间的11种显著的表观遗传相互作用与生存相关，这些相互作用靶向E2 F3、CCND 1、UTP 6、CDADC 1、SLC 35 E3、METRNL、TPCN 2、NACC 2、VGLL 4和PTEN。为此，TCGA膀胱癌数据的探索确定了与膀胱癌生存相关的表观遗传相互作用作为潜在的预后标志物。考虑到表观遗传事件在膀胱癌中的重要性和普遍性，现在是进一步了解不同表观遗传成分如何相互作用和相互影响的时候了。本文的在线版本（doi：10.1186/s12920-017-0269-y）包含补充材料，可供授权用户使用。
One of the fundamental challenges in cancer is to detect the regulators of gene expression changes during cancer progression. Through transcriptional silencing of critical cancer-related genes, epigenetic change such as DNA methylation plays a crucial role in cancer. In addition, miRNA, another major component of epigenome, is also a regulator at the post-transcriptional levels that modulate transcriptome changes. However, a mechanistic role of synergistic interactions between DNA methylation and miRNA as epigenetic regulators on transcriptomic changes and its association with clinical outcomes such as survival have remained largely unexplored in cancer. In this study, we propose an integrative framework to identify epigenetic interactions between methylation and miRNA associated with transcriptomic changes. To test the utility of the proposed framework, the bladder cancer data set, including DNA methylation, miRNA expression, and gene expression data, from The Cancer Genome Atlas (TCGA) was analyzed for this study. First, we found 120 genes associated with interactions between the two epigenomic components. Then, 11 significant epigenetic interactions between miRNA and methylation, which target E2F3, CCND1, UTP6, CDADC1, SLC35E3, METRNL, TPCN2, NACC2, VGLL4, and PTEN, were found to be associated with survival. To this end, exploration of TCGA bladder cancer data identified epigenetic interactions that are associated with survival as potential prognostic markers in bladder cancer. Given the importance and prevalence of these interactions of epigenetic events in bladder cancer it is timely to understand further how different epigenetic components interact and influence each other. The online version of this article (doi:10.1186/s12920-017-0269-y) contains supplementary material, which is available to authorized users.