Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Center for Computational Systems Medicine, School of Biomedical Informatics, The University of Texas Health Science Center, Houston, Texas.
J Cell Biochem. 2020 Mar;121(3):2406-2415. doi: 10.1002/jcb.29463. Epub 2019 Nov 6.
The long noncoding RNAs (lncRNAs) are associated with tumorigenesis and progression of cancer. While DNA methylation is a common epigenetic regulator of gene expression, the methylation of lncRNAs was rarely studied. To address this gap, we integrated DNA methylation and RNA-seq data to characterize the landscape of lncRNA methylation in colon adenocarcinoma (COAD). We collected and analyzed the lncRNA expression and methylation data from The Cancer Genome Atlas and Cancer Cell Line Encyclopedia to identify the epigenetically regulated lncRNAs. We further investigated the biological and clinical relevance of the identified lncRNAs via bioinformatics analysis. We identified 20 epigenetically upregulated lncRNAs in COAD, including several well-studied lncRNAs whose methylation regulation were poorly investigated, such as PVT1 and UCA1. We also revealed several novel tumor-associated lncRNAs in COAD, including GATA2-As1 and CYTOR. Next, we explored their biology function using gene set enrichment analysis and competitive endogenous RNA analysis. We characterized the methylation landscape of lncRNA in COAD and identified 20 epigenetically upregulated lncRNAs. Our findings will shed new light on the epigenetic regulation of lncRNA expression by DNA methylation.
长链非编码 RNA(lncRNA)与肿瘤的发生和发展有关。虽然 DNA 甲基化是基因表达的常见表观遗传调控因子,但 lncRNA 的甲基化很少被研究。为了解决这一空白,我们整合了 DNA 甲基化和 RNA-seq 数据,以描绘结肠癌(COAD)中 lncRNA 甲基化的全景。我们收集并分析了来自癌症基因组图谱和癌症细胞系百科全书的 lncRNA 表达和甲基化数据,以鉴定受表观遗传调控的 lncRNA。我们通过生物信息学分析进一步研究了鉴定出的 lncRNA 的生物学和临床相关性。我们在 COAD 中确定了 20 个表观遗传上调的 lncRNA,其中包括几个经过充分研究但甲基化调控研究甚少的 lncRNA,如 PVT1 和 UCA1。我们还在 COAD 中发现了几个新的肿瘤相关 lncRNA,包括 GATA2-As1 和 CYTOR。接下来,我们使用基因集富集分析和竞争性内源 RNA 分析探索了它们的生物学功能。我们描绘了 COAD 中 lncRNA 的甲基化全景,并确定了 20 个表观遗传上调的 lncRNA。我们的发现将为 DNA 甲基化对 lncRNA 表达的表观遗传调控提供新的见解。