Song Peng, Wu Lei, Guan Wenxian
Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Genet. 2020 Feb 27;11:91. doi: 10.3389/fgene.2020.00091. eCollection 2020.
Abnormal DNA methylation, an epigenetic modification, has increasingly been linked to the pathogenesis of many human cancers. However, there has been little focus on the DNA methylation patterns of genes encoding long noncoding RNAs (lncRNAs) in gastric cancer (GC). This study comprehensively determined DNA methylation and lncRNA expression profiles in GC through genome-wide analysis. Differentially methylated loci and lncRNAs were identified by integrating multi-omics data. In total, 548 differentially methylated CpG sites in lncRNA promoters and 2,399 differentially expressed lncRNAs were screened that were capable of distinguishing GC from normal tissues. Among them, 22 differentially methylation sites in 17 lncRNAs were inversely related to expression levels. Further analysis of DNA methylation status and gene expression level in GC revealed that three CpG sites (cg01550148, cg22497867, and cg20001829) and two lncRNAs (RP11-366F6.2 and RP5-881L22.5) were significantly associated with GC patient overall survival. Molecular function analysis showed that these abnormally methylated lncRNAs were mainly involved in transcriptional activator activity. Our study identified several lncRNAs regulated by aberrant DNA methylation that have clinical utility as novel prognostic biomarkers in GC. These findings help improve the understanding of methylated patterns of lncRNAs and further our knowledge of the role of epigenetics in cancer development.
异常的DNA甲基化作为一种表观遗传修饰，越来越多地与多种人类癌症的发病机制相关联。然而，胃癌（GC）中编码长链非编码RNA（lncRNA）的基因的DNA甲基化模式却很少受到关注。本研究通过全基因组分析全面确定了GC中的DNA甲基化和lncRNA表达谱。通过整合多组学数据鉴定了差异甲基化位点和lncRNA。总共筛选出了lncRNA启动子中的548个差异甲基化CpG位点和2399个差异表达的lncRNA，它们能够区分GC和正常组织。其中，17个lncRNA中的22个差异甲基化位点与表达水平呈负相关。对GC中DNA甲基化状态和基因表达水平的进一步分析表明，三个CpG位点（cg01550148、cg22497867和cg20001829）和两个lncRNA（RP11 - 366F6.2和RP5 - 881L22.5）与GC患者的总生存期显著相关。分子功能分析表明，这些异常甲基化的lncRNA主要参与转录激活活性。我们的研究鉴定了几种受异常DNA甲基化调控的lncRNA，它们作为GC中的新型预后生物标志物具有临床应用价值。这些发现有助于提高对lncRNA甲基化模式的理解，并进一步加深我们对表观遗传学在癌症发展中作用的认识。
