Zhi Hui, Ning Shangwei, Li Xiang, Li Yuyun, Wu Wei, Li Xia
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Nucleic Acids Res. 2014 Jul;42(13):8258-70. doi: 10.1093/nar/gku575. Epub 2014 Jul 10.
Despite growing consensus that long intergenic non-coding ribonucleic acids (lincRNAs) are modulators of cancer, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of lincRNAs in cancers remains limited. In this study, we constructed DNA methylation profiles for 4629 tumors and 705 normal tissue samples from 20 different types of human cancer by reannotating data of DNA methylation arrays. We found that lincRNAs had different promoter methylation patterns in cancers. We classified 2461 lincRNAs into two categories and three subcategories, according to their promoter methylation patterns in tumors. LincRNAs with resistant methylation patterns in tumors had conserved transcriptional regulation regions and were ubiquitously expressed across normal tissues. By integrating cancer subtype data and patient clinical information, we identified lincRNAs with promoter methylation patterns that were associated with cancer status, subtype or prognosis for several cancers. Network analysis of aberrantly methylated lincRNAs in cancers showed that lincRNAs with aberrant methylation patterns might be involved in cancer development and progression. The methylated and demethylated lincRNAs identified in this study provide novel insights for developing cancer biomarkers and potential therapeutic targets.
尽管人们越来越一致地认为长链基因间非编码核糖核酸（lincRNA）是癌症的调节因子，但关于癌症中lincRNA的脱氧核糖核酸（DNA）甲基化模式的知识仍然有限。在本研究中，我们通过重新注释DNA甲基化阵列数据，构建了来自20种不同类型人类癌症的4629个肿瘤和705个正常组织样本的DNA甲基化图谱。我们发现lincRNA在癌症中具有不同的启动子甲基化模式。根据它们在肿瘤中的启动子甲基化模式，我们将2461个lincRNA分为两类和三个亚类。在肿瘤中具有抗性甲基化模式的lincRNA具有保守的转录调控区域，并且在正常组织中普遍表达。通过整合癌症亚型数据和患者临床信息，我们确定了具有与几种癌症的癌症状态、亚型或预后相关的启动子甲基化模式的lincRNA。对癌症中异常甲基化的lincRNA进行网络分析表明，具有异常甲基化模式的lincRNA可能参与癌症的发生和发展。本研究中鉴定出的甲基化和去甲基化lincRNA为开发癌症生物标志物和潜在治疗靶点提供了新的见解。
