Whole-Transcriptome RNA Sequencing Reveals Significant Differentially Expressed mRNAs, miRNAs, and lncRNAs and Related Regulating Biological Pathways in the Peripheral Blood of COVID-19 Patients.
Whole-Transcriptome RNA Sequencing Reveals Significant Differentially Expressed mRNAs, miRNAs, and lncRNAs and Related Regulating Biological Pathways in the Peripheral Blood of COVID-19 Patients.
复制标题
DOI：
10.1155/2021/6635925
复制
发表时间：
2021
影响因子：
4.6
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Li CX;Chen J;Lv SK;Li JH;Li LL;Hu X
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）最初在中国被发现，目前在全球传播，导致了2019年冠状病毒病（COVID-19）大流行。值得注意的是，COVID-19的特点是全身性炎症。然而，COVID-19“细胞因子风暴”的潜在机制仍然有限。本研究收集了来自COVID-19患者（n = 10）和健康献血者（n = 4）的14份外周血样本，进行全转录组测序。COVID-19患者肺组织(70%)呈现磨玻璃样混浊。与对照组相比，新冠肺炎患者白细胞和淋巴细胞明显减少（p < 0.05）。与健康对照组相比，在COVID-19样本中共鉴定出25,482种差异表达的信使rna (DE mRNA)， 23种差异表达的microrna （DE miRNA）和410种差异表达的长链非编码rna （DE lncrna）。基因本体（Gene Ontology， GO）分析显示，表达上调的DE mrna主要参与抗原加工和内源性抗原呈递、T细胞介导的细胞毒性正调控、γ - δ T细胞活化正调控。下调的DE mrna主要集中在糖原生物合成过程中。我们还建立了上调/下调DE mrna的蛋白-蛋白相互作用（PPI）网络，并鉴定了4个模块。功能富集分析表明，这些模块靶点与细胞因子产生、细胞因子介导的信号通路、白细胞分化和迁移的正调控有关。在PPI模块网络中共筛选出6个枢纽基因，包括AKT1、TNFRSF1B、FCGR2A、CXCL8、STAT3和TLR2。此外，一个竞争性的内源性RNA网络显示了lncrna、mrna和mirna之间的相互作用。我们的研究结果强调了MSTRG.119845.30/hsa-miR-20a-5p/TNFRSF1B、MSTRG.119845.30/hsa-miR-29b-2-5p/FCGR2A和MSTRG.106112.2/hsa-miR-6501-5p/STAT3轴等细胞因子过量产生的潜在发病机制，这些细胞因子也可能在2019冠状病毒病患者毛玻璃不透明的发展中发挥重要作用。本研究对编码和非编码rna在COVID-19中的炎症调节机制有了新的认识，可能为COVID-19患者提供新的诊断生物标志物和治疗途径。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in China and currently worldwide dispersed, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Notably, COVID-19 is characterized by systemic inflammation. However, the potential mechanisms of the “cytokine storm” of COVID-19 are still limited. In this study, fourteen peripheral blood samples from COVID-19 patients (n = 10) and healthy donors (n = 4) were collected to perform the whole-transcriptome sequencing. Lung tissues of COVID-19 patients (70%) presenting with ground-glass opacity. Also, the leukocytes and lymphocytes were significantly decreased in COVID-19 compared with the control group (p < 0.05). In total, 25,482 differentially expressed messenger RNAs (DE mRNA), 23 differentially expressed microRNAs (DE miRNA), and 410 differentially expressed long noncoding RNAs (DE lncRNAs) were identified in the COVID-19 samples compared to the healthy controls. Gene Ontology (GO) analysis showed that the upregulated DE mRNAs were mainly involved in antigen processing and presentation of endogenous antigen, positive regulation of T cell mediated cytotoxicity, and positive regulation of gamma-delta T cell activation. The downregulated DE mRNAs were mainly concentrated in the glycogen biosynthetic process. We also established the protein-protein interaction (PPI) networks of up/downregulated DE mRNAs and identified 4 modules. Functional enrichment analyses indicated that these module targets were associated with positive regulation of cytokine production, cytokine-mediated signaling pathway, leukocyte differentiation, and migration. A total of 6 hub genes were selected in the PPI module networks including AKT1, TNFRSF1B, FCGR2A, CXCL8, STAT3, and TLR2. Moreover, a competing endogenous RNA network showed the interactions between lncRNAs, mRNAs, and miRNAs. Our results highlight the potential pathogenesis of excessive cytokine production such as MSTRG.119845.30/hsa-miR-20a-5p/TNFRSF1B, MSTRG.119845.30/hsa-miR-29b-2-5p/FCGR2A, and MSTRG.106112.2/hsa-miR-6501-5p/STAT3 axis, which may also play an important role in the development of ground-glass opacity in COVID-19 patients. This study gives new insights into inflammation regulatory mechanisms of coding and noncoding RNAs in COVID-19, which may provide novel diagnostic biomarkers and therapeutic avenues for COVID-19 patients.
登录
查看更多内容
影响因子：
12.7
作者：
Okabayashi, T;Kariwa, H;Fujii, N
通讯作者：
Fujii, N
影响因子：
10.5
作者：
Fehr AR;Channappanavar R;Perlman S
通讯作者：
Perlman S
影响因子：
4.8
作者：
Pinno, Jessica;Bongartz, Hannes;Dittrich, Anna
通讯作者：
Dittrich, Anna
影响因子：
4.6
作者：
Min CK;Cheon S;Ha NY;Sohn KM;Kim Y;Aigerim A;Shin HM;Choi JY;Inn KS;Kim JH;Moon JY;Choi MS;Cho NH;Kim YS
通讯作者：
Kim YS
影响因子：
3
作者：
Bader, GD;Hogue, CW
通讯作者：
Hogue, CW