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lncRNA 表达谱及冠心病患者心外膜脂肪组织中相关 ceRNA 网络分析。

lncRNA expression profiles and associated ceRNA network analyses in epicardial adipose tissue of patients with coronary artery disease.

机构信息

Department of Cardiovascular Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, People's Republic of China.

Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

出版信息

Sci Rep. 2021 Jan 15;11(1):1567. doi: 10.1038/s41598-021-81038-5.

DOI:10.1038/s41598-021-81038-5
PMID:33452392
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7810858/
Abstract

Epicardial adipose tissue (EAT) contributes to the pathophysiological process of coronary artery disease (CAD). The expression profiles of long non-coding RNAs (lncRNA) in EAT of patients with CAD have not been well characterized. We conducted high-throughput RNA sequencing to analyze the expression profiles of lncRNA in EAT of patients with CAD compared to patients without CAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed to investigate the principal functions of the significantly dysregulated mRNAs. We confirmed a dysregulated intergenic lncRNA (lincRNA) (LINC00968) by real-time quantitative PCR (RT-qPCR). Subsequently, we constructed a ceRNA network associated with LINC00968, which included 49 mRNAs. Compared with the control group, lncRNAs and genes of EAT in CAD were characterized as metabolic active and pro-inflammatory profiles. The sequencing analysis detected 2539 known and 1719 novel lncRNAs. Then, we depicted both lncRNA and gene signatures of EAT in CAD, featuring dysregulation of genes involved in metabolism, nuclear receptor transcriptional activity, antigen presentation, chemokine signaling, and inflammation. Finally, we identified a ceRNA network as candidate modulator in EAT and its potential role in CAD. We showed the expression profiles of specific EAT lncRNA and mRNA in CAD, and a selected non-coding associated ceRNA regulatory network, which taken together, may contribute to a better understanding of CAD mechanism and provide potential therapeutic targets.Trial registration Chinese Clinical Trial Registry, No. ChiCTR1900024782.

摘要

心外膜脂肪组织 (EAT) 参与冠状动脉疾病 (CAD) 的病理生理过程。CAD 患者 EAT 中长链非编码 RNA (lncRNA) 的表达谱尚未得到很好的描述。我们进行了高通量 RNA 测序,以分析与无 CAD 患者相比 CAD 患者 EAT 中 lncRNA 的表达谱。执行基因本体论 (GO) 和京都基因与基因组百科全书 (KEGG) 途径富集分析,以研究显著失调的 mRNAs 的主要功能。我们通过实时定量 PCR (RT-qPCR) 验证了一个失调的基因间 lncRNA (lncRNA) (LINC00968)。随后,我们构建了一个与 LINC00968 相关的 ceRNA 网络,其中包含 49 个 mRNAs。与对照组相比,CAD 患者 EAT 的 lncRNA 和基因表现为代谢活跃和促炎表型。测序分析检测到 2539 个已知和 1719 个新的 lncRNA。然后,我们描绘了 CAD 患者 EAT 的 lncRNA 和基因特征,其特征是代谢、核受体转录活性、抗原呈递、趋化因子信号和炎症相关基因的失调。最后,我们确定了一个 ceRNA 网络作为 EAT 的候选调节剂及其在 CAD 中的潜在作用。我们显示了 CAD 中特定 EAT lncRNA 和 mRNA 的表达谱,以及一个选定的非编码相关 ceRNA 调节网络,这些可能有助于更好地理解 CAD 机制,并提供潜在的治疗靶点。试验注册 中国临床试验注册中心,注册号 ChiCTR1900024782。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/821f8d45409b/41598_2021_81038_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/9877f28144b3/41598_2021_81038_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/821f8d45409b/41598_2021_81038_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/9877f28144b3/41598_2021_81038_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/779b7eeed1e4/41598_2021_81038_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/fec0dff1429b/41598_2021_81038_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/6fe01333bdbb/41598_2021_81038_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/568b/7810858/821f8d45409b/41598_2021_81038_Fig5_HTML.jpg

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