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冠心病患者外周血单个核细胞中的长链非编码RNA表达谱

Long non-coding RNA expression profiles in peripheral blood mononuclear cells of patients with coronary artery disease.

作者信息

Zhong Wei, Deng Qiaoting, Deng Xunwei, Zhong Zhixiong, Hou Jingyuan

机构信息

Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, Meizhou, China.

Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases, Meizhou, China.

出版信息

J Thorac Dis. 2020 Nov;12(11):6813-6825. doi: 10.21037/jtd-20-3105.

Abstract

BACKGROUND

Coronary artery disease (CAD) is a leading cause of death and often presents as a complex systemic disease. The aim of the presents study was to determine the expression profiles of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMC) of CAD patients and controls.

METHODS

The lncRNA expression profiling of PBMC obtained from 40 CAD patients and 10 non-obstructive coronary atherosclerosis (NOCA) subjects were analyzed using the Illumina Hiseq 4000 sequencer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed lncRNAs. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of mRNA were conducted to predict biologic functions.

RESULTS

Our results indicated that lncRNAs were differentially expressed; 83 were upregulated lncRNAs and 114 were downregulated lncRNAs (P<0.05). A horizontal comparison of lncRNA expression indicated that the change in the expression profile of 48 lncRNAs was consistent with the degree of CAD. Six lncRNAs were validated using qRT-PCR, confirming the accuracy of the RNA sequencing analysis. GO analysis indicated that these dysregulated lncRNA transcripts were related to chromatin organization, cell and cell part, and protein heterodimerization activity. Pathway analysis indicated that these differentially expressed genes mainly included viral carcinogenesis, systemic lupus erythematosus and alcoholism.

CONCLUSIONS

Our preliminary findings indicate that lncRNAs could be used as potential biomarkers of subclinical cardiac abnormalities in the PBMC of CAD patients. However, further studies are needed to verify our findings and hypothesis.

摘要

背景

冠状动脉疾病(CAD)是主要的死亡原因,常表现为一种复杂的全身性疾病。本研究的目的是确定CAD患者和对照组外周血单个核细胞(PBMC)中长链非编码RNA(lncRNA)的表达谱。

方法

使用Illumina Hiseq 4000测序仪分析从40例CAD患者和10例非阻塞性冠状动脉粥样硬化(NOCA)受试者获得的PBMC的lncRNA表达谱。采用定量实时聚合酶链反应(qRT-PCR)验证差异表达的lncRNA。对mRNA进行基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路富集分析以预测生物学功能。

结果

我们的结果表明lncRNA存在差异表达;83个lncRNA上调,1个lncRNA下调(P<0.05)。lncRNA表达的横向比较表明,48个lncRNA的表达谱变化与CAD程度一致。使用qRT-PCR验证了6个lncRNA,证实了RNA测序分析的准确性。GO分析表明,这些失调的lncRNA转录本与染色质组织、细胞和细胞部分以及蛋白质异二聚体化活性有关。通路分析表明,这些差异表达的基因主要包括病毒致癌作用、系统性红斑狼疮和酒精中毒。

结论

我们的初步研究结果表明,lncRNA可作为CAD患者PBMC中亚临床心脏异常的潜在生物标志物。然而,需要进一步研究来验证我们的发现和假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f48f/7711381/4bf5eab69ee5/jtd-12-11-6813-f1.jpg

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