Construction and Analysis of a ceRNA Network in Cardiac Fibroblast During Fibrosis Based on in vivo and in vitro Data.
Construction and Analysis of a ceRNA Network in Cardiac Fibroblast During Fibrosis Based on in vivo and in vitro Data.
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基于体内外数据的心脏成纤维细胞纤维化过程中ceRNA网络的构建和分析
DOI：
10.3389/fgene.2020.503256
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发表时间：
2020
影响因子：
3.7
通讯作者：
Chen YX
中科院分区：
文献类型：
--
作者：
Gao QY;Zhang HF;Chen ZT;Li YW;Wang SH;Wen ZZ;Xie Y;Mai JT;Wang JF;Chen YX
心脏成纤维细胞（CF）的活化是心脏纤维化的关键。我们构建了一个与心脏成纤维细胞相关的竞争性内源性RNA（ceRNA）网络。探索了该ceRNA网络中“枢纽基因”与纤维化相关的潜在功能。在Gene Expression Omnibus数据库中搜索合格的数据集。鉴定了差异表达的信使（m）RNA（DE-mRNA）和长非编码（lnc）RNA（DE-lncRNA）。对microRNA进行了预测和验证。通过Cytoscape构建并可视化预测的ceRNA网络，并验证ceRNA串扰。进行单基因集富集分析（SGSEA），并使用比较毒理基因组学数据库（CTD）来分析ceRNA网络中DE-mRNA的最密切相关的途径和疾病。通过小干扰（si）RNA消除来验证DE-mRNA和DE-lncRNA在ceRNA网络中的功能。使用GSE 97358和GSE 116250数据集（分别描述了人心脏成纤维细胞和衰竭心室中差异表达的基因）进行分析。在GSE 97358和GSE 116250数据集中分别鉴定了420个DE-mRNA和39个DE-lncRNA，以及369个DE-mRNA和93个DE-lncRNA。大多数基因与信号转导、细胞因子活性和细胞增殖有关。13个具有相同表达趋势的DE-mRNA在两个数据集中重叠。预测了23种候选microRNA，其中11种表达不同。只有两个DE-lncRNA与11种microRNA中的任何一种配对。最后，两种mRNA [ADAM金属肽酶结构域19（ADAM 19）和转化生长因子β诱导（TGFBI）]、三种microRNA（miR-9- 5 p、miR-124- 3 p和miR-153- 3 p）和两种lncRNA（LINC 00511和SNHG 15）构成了我们的ceRNA网络。针对LINC 00511的siRNA增加了miR-124- 3 p和miR-9- 5 p的表达，并降低了ADAM 19和TGFBI的表达，而针对SNHG 15的siRNA增加了miR-153- 3 p并降低了ADAM 19的表达。SGSEA和CTD分别显示ADAM 19和TGFBI与TGF-β1通路和心脏纤维化密切相关。两种mRNA或两种lncRNA的缺失可减轻CF的激活。CF特异性ceRNA网络包括2个lncRNA、3个miRNA和2个mRNA，在心脏纤维化过程中发挥重要作用，为该领域的研究提供了潜在的靶基因。
Activation of cardiac fibroblasts (CF) is crucial to cardiac fibrosis. We constructed a cardiac fibroblast-related competing endogenous RNA (ceRNA) network. Potential functions related to fibrosis of “hub genes” in this ceRNA network were explored. The Gene Expression Omnibus database was searched for eligible datasets. Differentially expressed messenger (m)RNA (DE-mRNA) and long non-coding (lnc)RNA (DE-lncRNA) were identified. microRNA was predicted and validated. A predicted ceRNA network was constructed and visualized by Cytoscape, and ceRNA crosstalk was validated. A Single Gene Set Enrichment Analysis (SGSEA) was done, and the Comparative Toxicogenomics Database (CTD) was employed to analyze the most closely associated pathways and diseases of DE-mRNA in the ceRNA network. The functions of DE-mRNA and DE-lncRNA in the ceRNA network were validated by small interfering (si)RNA depletion. The GSE97358 and GSE116250 datasets (which described differentially expressed genes in human cardiac fibroblasts and failing ventricles, respectively) were used for analyses. Four-hundred-and-twenty DE-mRNA and 39 DE-lncRNA, and 369 DE-mRNA and 93 DE-lncRNA were identified, respectively, in the GSE97358 and GSE116250 datasets. Most of the genes were related to signal transduction, cytokine activity, and cell proliferation. Thirteen DE-mRNA with the same expression tendency were overlapped in the two datasets. Twenty-three candidate microRNAs were predicted and the expression of 11 were different. Only two DE-lncRNA were paired to any one of 11 microRNA. Finally, two mRNA [ADAM metallopeptidase domain 19, (ADAM19) and transforming growth factor beta induced, (TGFBI)], three microRNA (miR-9-5p, miR-124-3p, and miR-153-3p) and two lncRNA (LINC00511 and SNHG15) constituted our ceRNA network. siRNA against LINC00511 increased miR-124-3p and miR-9-5p expression, and decreased ADAM19 and TGFBI expression, whereas siRNA against SNHG15 increased miR-153-3p and decreased ADAM19 expression. ADAM19 and TGFBI were closely related to the TGF-β1 pathway and cardiac fibrosis, as shown by SGSEA and CTD, respectively. Depletion of two mRNA or two lncRNA could alleviate CF activation. The CF-specific ceRNA network, including two lncRNA, three miRNA, and two mRNA, played a crucial role during cardiac fibrosis, which provided potential target genes in this field.
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影响因子：
5.8
作者：
Keating, Dominic T.;Sadlier, Denise M.;Patricelli, Andrea;Smith, Sinead M.;Walls, Dermot;Egan, Jim J.;Doran, Peter P.
通讯作者：
Doran, Peter P.
影响因子：
8
作者：
Kong, Ping;Christia, Panagiota;Frangogiannis, Nikolaos G.
通讯作者：
Frangogiannis, Nikolaos G.
DOI：
10.1161/circimaging.115.004325
发表时间：
2016-08
期刊：
Circulation. Cardiovascular imaging
影响因子：
--
作者：
Jordan JH;Vasu S;Morgan TM;D'Agostino RB Jr;Meléndez GC;Hamilton CA;Arai AE;Liu S;Liu CY;Lima JA;Bluemke DA;Burke GL;Hundley WG
通讯作者：
Hundley WG
影响因子：
14.9
作者：
Davis AP;Grondin CJ;Johnson RJ;Sciaky D;McMorran R;Wiegers J;Wiegers TC;Mattingly CJ
通讯作者：
Mattingly CJ
从受体到 Smads 的 TGF-β 信号传导
影响因子：
7.2
作者：
Hata A;Chen YG
通讯作者：
Chen YG