Identification of circulating hub long noncoding RNAs associated with hypertrophic cardiomyopathy using weighted correlation network analysis.
Identification of circulating hub long noncoding RNAs associated with hypertrophic cardiomyopathy using weighted correlation network analysis.
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使用加权相关网络分析鉴定与肥厚型心肌病相关的循环中枢长非编码RNA
DOI：
10.3892/mmr.2020.11566
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发表时间：
2020-12
影响因子：
3.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Guo Q;Wang J;Sun R;Gu W;He Z;Chen Q;Liu W;Chen Y;Wang J;Zhang Y
肥厚型心肌病（HCM）是最常见的遗传性心脏病之一，也是青少年和年轻人心脏性猝死的主要原因。循环中的长链非编码RNA（lncRNA）已被证明是多种心血管疾病的诊断和治疗靶点。然而，HCM患者的循环细胞外lncRNA表达谱仍不清楚。使用人类lncRNA微阵列评估HCM患者和健康对照的血浆lncRNA表达。使用加权相关网络分析（WGCNA）和微阵列数据的线性模型（Limma）。对基因表达综合数据库中来自心脏组织的GSE 68316数据进行分析以进一步验证。使用WGCNA，两个模块（称为洋红色和浅黄色模块）被确定为与HCM呈正相关。基因本体分析显示，在洋红色模块中的lncRNA靶向“心脏生长”。使用Limma，与对照组相比，HCM患者血浆中共有290种lncRNA差异表达（210种上调，80种下调）。此外，结合WGCNA和Limma分析表明，与对照相比，洋红色模块中的27个中心lncRNA和浅黄色模块中的13个中心lncRNA显著上调。此外，在两个模块中鉴定的40种差异表达的枢纽lncRNA中，三种循环lncRNA（lnc-P2 RY 6 -1：1、ENST 00000488040和ENST 0000588047）在HCM心脏组织验证数据集中也显著上调。这些lncRNA可作为HCM精确诊断和治疗的生物标志物和治疗靶点。
Hypertrophic cardiomyopathy (HCM) is one of the most commonly inherited heart diseases and the leading cause of sudden cardiac death among adolescents and young adults. Circulating long noncoding RNAs (lncRNAs) have demonstrated potential as diagnostic and therapeutic targets in several cardiovascular diseases. However, the circulating extracellular lncRNA expression profile of patients with HCM remains unclear. Plasma lncRNA expression was evaluated in patients with HCM and healthy controls using a human lncRNA microarray. A weighted correlation network analysis (WGCNA) and linear models for microarray data (Limma) were used. GSE68316 data from cardiac tissue in the Gene Expression Omnibus database were analysed for further validation. Using WGCNA, two modules (referred to as the magenta and the light-yellow module) were identified that were positively associated with HCM. Gene Ontology analysis revealed that lncRNAs in the magenta module targeted ‘heart growth’. Using Limma, a total of 290 lncRNAs were differentially expressed (210 upregulated and 80 downregulated) in the plasma of HCM patients, compared with controls. Moreover, combined WGCNA and Limma analysis demonstrated that 27 hub lncRNAs in the magenta module and 13 hub lncRNAs in the light-yellow module were significantly upregulated, compared with the controls. Moreover, of the 40 differentially expressed hub lncRNAs identified in the two modules, three circulating lncRNAs (lnc-P2RY6-1:1, ENST00000488040 and ENST00000588047) were also significantly upregulated in the HCM cardiac tissue validation dataset. These lncRNAs may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of HCM.
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影响因子：
39.3
作者：
Elliott, Perry M.;Anastasakis, Aris;Watkins, Hugh
通讯作者：
Watkins, Hugh
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
20.1
作者：
Sallam T;Sandhu J;Tontonoz P
通讯作者：
Tontonoz P
影响因子：
3.8
作者：
Gomez, Juan;Lorca, Rebeca;Coto, Eliecer
通讯作者：
Coto, Eliecer