Transcriptomic and Proteomic Profiling of Human Stable and Unstable Carotid Atherosclerotic Plaques.
Transcriptomic and Proteomic Profiling of Human Stable and Unstable Carotid Atherosclerotic Plaques.
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DOI：
10.3389/fgene.2021.755507
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发表时间：
2021
影响因子：
3.7
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Bao MH;Zhang RQ;Huang XS;Zhou J;Guo Z;Xu BF;Liu R
动脉粥样硬化是一种慢性炎症性疾病，具有很高的患病率和死亡率。动脉粥样硬化斑块破裂是动脉粥样硬化临床事件的主要原因。明确稳定斑块和不稳定斑块的转录组和蛋白质组差异对预防临床表现至关重要。在本研究中，5个稳定和5个不稳定的人颈动脉粥样硬化斑块获得了颈动脉内膜切除术。通过使用Illumina HiSeq的下一代测序将样品用于全转录组测序（RNA-Seq），并通过HPLC-MS/MS用于蛋白质组分析。通过分析它们的位置和序列来鉴定lncRNA靶向基因和circRNA起源基因。利用基因本体论和KEGG富集技术对差异表达的RNA和蛋白质进行功能分析。利用在线工具STRING构建了蛋白质相互作用（PPI）网络。分析转录组和蛋白质组的一致性，预测lncRNA/circRNA-miRNA-mRNA相互作用。结果，202个mRNA、488个lncRNA、91个circRNA和293个蛋白质被鉴定为在稳定和不稳定的动脉粥样硬化斑块之间差异表达。488个lncRNA可能通过顺式作用机制靶向381个蛋白质编码基因。序列分析表明，91个差异表达的circRNA分别来自97个蛋白质编码基因。这些差异表达的RNA和蛋白质主要集中在细胞对应激或刺激的反应、基因转录调控、免疫反应、神经系统功能、血液学活动和内分泌系统等方面。这些结果与数据集GSE 41571中先前报告的数据一致。进一步的分析确定了CD 5L、S100 A12、CKB（lncRNA MSTRG.11455.17的靶基因）、CEMIP（lncRNA MSTRG.12845的靶基因）和SH 3GLB 1（hsacirc_000411的起源基因）是调节动脉粥样硬化斑块稳定性的关键基因。我们的研究结果提供了一个全面的转录组学和蛋白质组学知识的稳定性动脉粥样硬化斑块。
Atherosclerosis is a chronic inflammatory disease with high prevalence and mortality. The rupture of atherosclerotic plaque is the main reason for the clinical events caused by atherosclerosis. Making clear the transcriptomic and proteomic profiles between the stabe and unstable atherosclerotic plaques is crucial to prevent the clinical manifestations. In the present study, 5 stable and 5 unstable human carotid atherosclerotic plaques were obtained by carotid endarterectomy. The samples were used for the whole transcriptome sequencing (RNA-Seq) by the Next-Generation Sequencing using the Illumina HiSeq, and for proteome analysis by HPLC-MS/MS. The lncRNA-targeted genes and circRNA-originated genes were identified by analyzing their location and sequence. Gene Ontology and KEGG enrichment was carried out to analyze the functions of differentially expressed RNAs and proteins. The protein-protein interactions (PPI) network was constructed by the online tool STRING. The consistency of transcriptome and proteome were analyzed, and the lncRNA/circRNA-miRNA-mRNA interactions were predicted. As a result, 202 mRNAs, 488 lncRNAs, 91 circRNAs, and 293 proteins were identified to be differentially expressed between stable and unstable atherosclerotic plaques. The 488 lncRNAs might target 381 protein-coding genes by cis-acting mechanisms. Sequence analysis indicated the 91 differentially expressed circRNAs were originated from 97 protein-coding genes. These differentially expressed RNAs and proteins were mainly enriched in the terms of the cellular response to stress or stimulus, the regulation of gene transcription, the immune response, the nervous system functions, the hematologic activities, and the endocrine system. These results were consistent with the previous reported data in the dataset GSE41571. Further analysis identified CD5L, S100A12, CKB (target gene of lncRNA MSTRG.11455.17), CEMIP (target gene of lncRNA MSTRG.12845), and SH3GLB1 (originated gene of hsacirc_000411) to be critical genes in regulating the stability of atherosclerotic plaques. Our results provided a comprehensive transcriptomic and proteomic knowledge on the stability of atherosclerotic plaques.
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