The landscape of DNA methylation-mediated regulation of long non-coding RNAs in breast cancer.
The landscape of DNA methylation-mediated regulation of long non-coding RNAs in breast cancer.
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DOI：
10.18632/oncotarget.17705
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Zhang C;Wang X;Li X;Zhao N;Wang Y;Han X;Ci C;Zhang J;Li M;Zhang Y
尽管系统的研究已经确定了许多与乳腺癌有关的长链非编码rna (lncrna)，但关于这些lncrna甲基化介导的失调的知识仍然有限。在这里，我们整合了多组学数据来分析lncrna在乳腺浸润性癌（BRCA）中的甲基化改变。我们发现lncrna在BRCA的启动子区域显示出不同的甲基化模式。根据lncrna在肿瘤和正常样本中的启动子甲基化模式和表达水平，将其分为两类和四个亚类。通过顺式调控分析和基因本体网络，鉴定出异常甲基化的lncrna与肿瘤调控、增殖或转录因子表达相关。竞争内源性RNA网络和异常甲基化lncRNAs的功能富集分析表明，具有不同甲基化模式的lncRNAs显著参与癌症的几种标志和KEGG通路。最后，基于网络中mRNA模块的生存分析显示，高甲基化沉默的lncrna与BRCA的预后显著相关。该研究增强了对lncrna异常甲基化模式的理解，并为识别乳腺癌的癌症生物标志物和潜在治疗靶点提供了新的见解。
Although systematic studies have identified a host of long non-coding RNAs (lncRNAs) which are involved in breast cancer, the knowledge about the methyla-tion-mediated dysregulation of those lncRNAs remains limited. Here, we integrated multi-omics data to analyze the methylated alteration of lncRNAs in breast invasive carcinoma (BRCA). We found that lncRNAs showed diverse methylation patterns on promoter regions in BRCA. LncRNAs were divided into two categories and four subcategories based on their promoter methylation patterns and expression levels be-tween tumor and normal samples. Through cis-regulatory analysis and gene ontology network, abnormally methylated lncRNAs were identified to be associated with can-cer regulation, proliferation or expression of transcription factors. Competing endog-enous RNA network and functional enrichment analysis of abnormally methylated lncRNAs showed that lncRNAs with different methylation patterns were involved in several hallmarks and KEGG pathways of cancers significantly. Finally, survival analysis based on mRNA modules in networks revealed that lncRNAs silenced by high methylation were associated with prognosis significantly in BRCA. This study enhances the understanding of aberrantly methylated patterns of lncRNAs and pro-vides a novel insight for identifying cancer biomarkers and potential therapeutic tar-gets in breast cancer.
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