Integrated Analysis of lncRNA-Mediated ceRNA Network in Lung Adenocarcinoma.
Integrated Analysis of lncRNA-Mediated ceRNA Network in Lung Adenocarcinoma.
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肺腺癌中 lncRNA 介导的 ceRNA 网络的综合分析
DOI：
10.3389/fonc.2020.554759
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发表时间：
2020
影响因子：
4.7
通讯作者：
Yu Z
中科院分区：
文献类型：
--
作者：
Wu X;Sui Z;Zhang H;Wang Y;Yu Z
越来越多的证据表明，长链非编码RNA（lncRNA）可以作为竞争性内源RNA（ceRNA）与microRNA（miRNAs）结合，从而影响和调控靶基因的表达。lncRNA-miRNA-mRNA ceRNA网络已被理论化为在许多类型的肿瘤中发挥不可或缺的作用。然而，lncRNA相关的ceRNA调控网络在肺腺癌（LUAD）中的作用仍不清楚。我们从The Cancer Genome Atlas（TCGA）数据门户下载了LUAD的RNAseq和miRNAseq数据，并使用R软件的edgeR包鉴定了LUAD与相应癌旁组织之间的差异表达lncRNA（DElncRNA）、差异表达miRNA（DEmiRNA）和差异表达mRNA（DEmRNAs）。基于miRcode、miRTarBase、miRDB和TargetScan数据库生成的相互作用，我们使用Cytoscape（3.7.2版）构建了lncRNA-miRNA-mRNA ceRNA网络。使用大卫6.8生物信息学资源进行基因本体（GO）注释和京都基因和基因组百科全书（KEGG）通路分析，并使用R.根据Kaplan-Meier曲线，应用R中的生存包评估基因对LUAD预后的影响。在LUAD中总共鉴定了1645个DElncRNA、117个DEmiRNA和2729个DEmRNA。LUAD特异性ceRNA网络由157个节点和378条边组成（329个DElncRNA-DEmiRNA相互作用和49个DEmiRNA-DEmRNA相互作用）。GO和KEGG通路注释表明LUAD特异性ceRNA网络与肿瘤相关的分子功能和通路有关。七种lncRNA（DISC 1-IT 1、SYNPR-AS 1、H19、LINC 00460、LINC 00518、DSCR 10和STEAP 2-AS 1），一种miRNA（hsa-mir-31）和16种mRNA（ATAD 2、OSCAR、KIF23、E2F7、PFKP、MCM4、CEP55、CBX 2、CCNE 1、CLSPN、CCNB 1、CDC 25 A、EZH2、CHEK 1、SLC7A11、和PBK）与总生存率显著相关。在这项研究中，我们描述了LUAD进展的潜在调控机制。我们提出了一个新的lncRNA-miRNA-mRNA ceRNA网络，可以帮助进一步探索LUAD的分子机制。
A growing body of evidence indicates that long non-coding RNAs (lncRNAs) can act as competitive endogenous RNAs (ceRNAs) to bind to microRNAs (miRNAs), thereby affecting and regulating the expression of target genes. The lncRNA–miRNA–mRNA ceRNA network has been theorized to play an indispensable role in many types of tumors. However, the role of the lncRNA-related ceRNA regulatory network in lung adenocarcinoma (LUAD) remains unclear. We downloaded the RNAseq and miRNAseq data of LUAD from The Cancer Genome Atlas (TCGA) data portal and identified differentially expressed lncRNAs (DElncRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) between LUAD and corresponding paracancerous tissues by using the edgeR package of R software. We constructed the lncRNA–miRNA–mRNA ceRNA network by using Cytoscape (version 3.7.2) on the basis of the interaction generated from the miRcode, miRTarBase, miRDB, and TargetScan databases. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed with DAVID 6.8 bioinformatics resources and plotted by using the ggplot2 package in R. The effect of genes on LUAD prognosis was assessed by applying the survival package in R in accordance with the Kaplan–Meier curve. In total, 1645 DElncRNAs, 117 DEmiRNAs, and 2729 DEmRNAs were identified in LUAD. The LUAD-specific ceRNA network was composed of 157 nodes and 378 edges (329 DElncRNA–DEmiRNA interactions and 49 DEmiRNA–DEmRNA interactions). GO and KEGG pathway annotations suggested that the LUAD-specific ceRNA network was related to tumor-related molecular functions and pathways. Seven lncRNAs (DISC1-IT1, SYNPR-AS1, H19, LINC00460, LINC00518, DSCR10, and STEAP2-AS1), one miRNA (hsa-mir-31), and 16 mRNAs (ATAD2, OSCAR, KIF23, E2F7, PFKP, MCM4, CEP55, CBX2, CCNE1, CLSPN, CCNB1, CDC25A, EZH2, CHEK1, SLC7A11, and PBK) were revealed to be significantly correlated with overall survival. In this study, we described the potential regulatory mechanism of the progression of LUAD. We proposed a new lncRNA–miRNA–mRNA ceRNA network that could help further explore the molecular mechanisms of LUAD.
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影响因子：
5.2
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