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急性心肌梗死患者外周血单个核细胞中长链非编码RNA和mRNA的表达谱

Expression profiles of long noncoding RNAs and mRNAs in peripheral blood mononuclear cells of patients with acute myocardial infarction.

作者信息

Zhao Pingsen, Wu Heming, Zhong Zhixiong, Zhang Qifeng, Zhong Wei, Li Bin, Li Cunren, Liu Zhidong, Yang Min

机构信息

Clinical Core Laboratory.

Center for Precision Medicine.

出版信息

Medicine (Baltimore). 2018 Oct;97(41):e12604. doi: 10.1097/MD.0000000000012604.

Abstract

Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic diseases. The incidence of AMI in some countries increases year by year, and shows younger trend. Some study indicated that abnormal expression of lncRNAs was closely related to cardiovascular disease. The aim of this study was to examine the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with AMI through controlled studies.In the present study, we examined the lncRNA and mRNA expression profiles in 8 patients with AMI, with 7 NCA (noncoronary artery) subjects as controls using RNA sequencing protocol (RNA-seq) on the Illumina HiSeq 4000 platform. The differentially expressed lncRNAs were selected for bioinformatic analysis including gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG). Quantitative real time PCR (qRT-PCR) was used to confirm the differential expression of lncRNAs.We kept about 11.29 gigabase (Gb) high-quality sequence data while the Q30 ranged from 94.39% to 95.19% for each sample. Compared to the lncRNA expression profiles of NCA controls, a total of 106 differentially expressed lncRNAs were discriminated in AMI patients, including 40 upregulated lncRNAs and 66 downregulated lncRNAs (P < .05). Among the genes corresponding to the identified mRNAs, 2905 genes are involved in biological processes, 339 in cellular components, and 501 in molecular functions. Based on the KEGG pathway analysis, the most enriched pathways corresponding to the differentially expressed lncRNAs were associated with systemic lupus erythematosus, alcoholism, oxidative phosphorylation, Parkinson's disease and viral carcinogenesis, and so on. Further, 3 upregulated and 3 downregulated lncRNAs were randomly selected for qRT-PCR verification and the results of qRT-PCR were consistent with the findings obtained from RNA sequencing analysis.As a result, differential expression profiles of lncRNAs in AMI were identified in our study. The results suggested that lncRNAs may play important roles in the biological and pathological processes of AMI. These findings may provide useful reference for the early diagnosis and risk stratification of AMI patients. To enlarge the sample size in the next step will be needed for further research to confirm our results.

摘要

急性心肌梗死(AMI)是冠状动脉粥样硬化疾病中最严重的类型。在一些国家,AMI的发病率逐年上升,且呈年轻化趋势。一些研究表明,长链非编码RNA(lncRNAs)的异常表达与心血管疾病密切相关。本研究旨在通过对照研究检测AMI患者外周血单个核细胞(PBMCs)中的lncRNA表达谱。在本研究中,我们在Illumina HiSeq 4000平台上使用RNA测序方案(RNA-seq)检测了8例AMI患者以及7例非冠状动脉(NCA)受试者作为对照的lncRNA和mRNA表达谱。选择差异表达的lncRNAs进行生物信息学分析,包括基因本体(GO)富集分析和京都基因与基因组百科全书通路(KEGG)分析。采用定量实时PCR(qRT-PCR)来确认lncRNAs的差异表达。每个样本保留了约11.29千兆碱基(Gb)的高质量序列数据,Q30范围为94.39%至95.19%。与NCA对照的lncRNA表达谱相比,在AMI患者中总共鉴别出106个差异表达的lncRNAs,包括40个上调的lncRNAs和66个下调的lncRNAs(P<0.05)。在所鉴定的mRNA对应的基因中,2905个基因参与生物过程,339个参与细胞成分,501个参与分子功能。基于KEGG通路分析,差异表达lncRNAs最富集的通路与系统性红斑狼疮、酒精中毒、氧化磷酸化、帕金森病和病毒致癌作用等相关。此外,随机选择3个上调和3个下调的lncRNAs进行qRT-PCR验证,qRT-PCR结果与RNA测序分析结果一致。结果,在我们的研究中确定了AMI中lncRNAs的差异表达谱。结果表明,lncRNAs可能在AMI的生物学和病理过程中发挥重要作用。这些发现可能为AMI患者的早期诊断和风险分层提供有用的参考。下一步需要扩大样本量以进行进一步研究来证实我们的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/33e3/6203524/b4235a0dca03/medi-97-e12604-g001.jpg

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