Feng Nannan, Wang Yu, Zheng Min, Yu Xiao, Lin Hongyan, Ma Rong-Na, Shi Oumin, Zheng Xiangqian, Gao Ming, Yu Herbert, Garmire Lana, Qian Biyun
Hongqiao International Institute of Medicine, Shanghai Tongren Hospital & Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Tianjin Key Laboratory of Cancer Prevention & Therapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China.
Epigenomics. 2017 Jan 23. doi: 10.2217/epi-2016-0120.
The goal of this study is to identify differentially methylated (DM) loci associated with long noncoding RNA (lncRNA)/mRNA expression in non-small-cell lung cancer (NSCLC).
MATERIALS & METHODS: Microarrays were used to interrogate genome-wide methylation and expression of lncRNA/mRNA in NSCLC.
We identified 113,644 DM loci between tumors and adjacent tissues. Among them, 26,310 DM loci were associated with 1685 differentially expressed genes, and 839 genes had significant correlations between methylation and expression, of which 26 hypermethylated loci in transcription start site 200 were correlated with low gene expression. We validated the correlations between methylation and expression in five genes (CDO1, C2orf40, SCARF1, ZFP106 and IFFO1) using pyrosequencing and quantitative polymerase chain reaction. We also found significant correlations between lncRNAs and mRNAs, and validated four of the correlations with quantitative polymerase chain reaction.
Integrated analysis of genome-wide DNA methylation and lncRNA/mRNA expression allows us to identify new DM loci-correlated with gene expression in NSCLC.
本研究的目的是鉴定与非小细胞肺癌（NSCLC）中长链非编码RNA（lncRNA）/信使核糖核酸（mRNA）表达相关的差异甲基化（DM）位点。
使用微阵列检测NSCLC中全基因组甲基化以及lncRNA/mRNA的表达。
我们在肿瘤组织和癌旁组织之间鉴定出113,644个DM位点。其中, 26,310个DM位点与1685个差异表达基因相关，839个基因的甲基化与表达之间存在显著相关性，其中转录起始位点200处的26个高甲基化位点与低基因表达相关。我们使用焦磷酸测序和定量聚合酶链反应验证了五个基因（CDO1、C2orf40、SCARF1、ZFP106和IFFO1）甲基化与表达之间的相关性。我们还发现lncRNA和mRNA之间存在显著相关性，并通过定量聚合酶链反应验证了其中四个相关性。
全基因组DNA甲基化和lncRNA/mRNA表达的综合分析使我们能够鉴定出与NSCLC基因表达相关的新DM位点。
