Yin Xunli, Wang Xuebing, Wang Shiai, Xia Youwei, Chen Huihui, Yin Ling, Hu Keqing
Department of Cardiovascular Medicine, The Seventh People's Hospital of Jinan, Jinan, 250100, People's Republic of China.
Department of Critical Care Medicine, The Seventh People's Hospital of Jinan, Jinan, 250100, People's Republic of China.
Int J Gen Med. 2022 Feb 18;15:1715-1731. doi: 10.2147/IJGM.S354359. eCollection 2022.
Acute myocardial infarction (AMI), which commonly leads to heart failure, is among the leading causes of mortality worldwide. The aim of this study was to find potential regulatory network for miRNA-inflammation, oxidative stress and prognosis-related mRNA to uncover molecular mechanisms of AMI.
The expression profiles of miRNA and mRNA in the blood samples from AMI patients were downloaded from the Gene Expression Omnibus (GEO) dataset for differential expression analysis. Weighted gene co-expression network analysis (WGCNA) was used to further identify important mRNAs. The negatively regulatory network construction of miRNA-inflammation, oxidative stress and prognosis-related mRNAs was performed, followed by protein-protein interaction (PPI) and functional analysis of mRNAs.
A total of three pairs of negatively regulatory network of miRNA-inflammation and prognosis-related mRNAs (hsa-miR-636/hsa-miR-491-3p/hsa-miR-188-5p/hsa-miR-188-3p-AQP9, hsa-miR-518a-3p-C5AR1 and hsa-miR-509-3-5p/hsa-miR-127-5p-PLAUR), two pairs of negatively regulatory network of miRNA-oxidative stress and prognosis-related mRNAs (hsa-miR-604-TLR4 and hsa-miR-139-5p-CXCL1) and three pairs of negatively regulatory network of miRNA-inflammation, oxidative stress and prognosis-related mRNA (hsa-miR-634/hsa-miR-591-TLR2, hsa-miR-938-NFKBIA and hsa-miR-520h/hsa-miR-450b-3p-ADM) were identified. In the KEGG analysis, some signaling pathways were identified, such as complement and coagulation cascades, pathogenic infection, chemokine signaling pathway and cytokine-cytokine receptor interaction and Toll-like receptor signaling pathway.
Identified negatively regulatory network of miRNA-inflammation/oxidative stress and prognosis-related mRNA may be involved in the process of AMI. Those inflammation/oxidative stress and prognosis-related mRNAs may be diagnostic and prognostic biomarkers for AMI.
急性心肌梗死(AMI)是全球主要死因之一,常导致心力衰竭。本研究旨在寻找miRNA-炎症、氧化应激和预后相关mRNA的潜在调控网络,以揭示AMI的分子机制。
从基因表达综合数据库(GEO)下载AMI患者血液样本中miRNA和mRNA的表达谱进行差异表达分析。采用加权基因共表达网络分析(WGCNA)进一步鉴定重要的mRNA。构建miRNA-炎症、氧化应激和预后相关mRNA的负调控网络,随后进行蛋白质-蛋白质相互作用(PPI)和mRNA的功能分析。
共鉴定出三对miRNA-炎症与预后相关mRNA的负调控网络(hsa-miR-636/hsa-miR-491-3p/hsa-miR-188-5p/hsa-miR-188-3p-AQP9、hsa-miR-518a-3p-C5AR1和hsa-miR-509-3-5p/hsa-miR-127-5p-PLAUR)、两对miRNA-氧化应激与预后相关mRNA的负调控网络(hsa-miR-604-TLR4和hsa-miR-139-5p-CXCL1)以及三对miRNA-炎症、氧化应激和预后相关mRNA的负调控网络(hsa-miR-634/hsa-miR-591-TLR2、hsa-miR-938-NFKBIA和hsa-miR-520h/hsa-miR-450b-3p-ADM)。在KEGG分析中,鉴定出一些信号通路,如补体和凝血级联反应、病原体感染、趋化因子信号通路、细胞因子-细胞因子受体相互作用以及Toll样受体信号通路。
鉴定出的miRNA-炎症/氧化应激与预后相关mRNA的负调控网络可能参与AMI的发生过程。这些炎症/氧化应激和预后相关mRNA可能是AMI的诊断和预后生物标志物。