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揭示急性心肌梗死向心肌纤维化再到心力衰竭进展过程中的潜在长链非编码RNA和信使核糖核酸

Uncovering Potential lncRNAs and mRNAs in the Progression From Acute Myocardial Infarction to Myocardial Fibrosis to Heart Failure.

作者信息

Wang Shuo, Wang Enmao, Chen Qincong, Yang Yan, Xu Lei, Zhang Xiaolei, Wu Rubing, Hu Xitian, Wu Zhihong

机构信息

Department of Cardiovasology, Shijiazhuang People's Hospital, Shijiazhuang, China.

出版信息

Front Cardiovasc Med. 2021 Jul 16;8:664044. doi: 10.3389/fcvm.2021.664044. eCollection 2021.

Abstract

Morbidity and mortality of heart failure (HF) post-myocardial infarction (MI) remain elevated. The aim of this study was to find potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis (MF) to HF. Firstly, blood samples from AMI, MF, and HF patients were used for RNA sequencing. Secondly, differentially expressed lncRNAs and mRNAs were obtained in MF vs. AMI and HF vs. MF, followed by functional analysis of shared differentially expressed mRNAs between two groups. Thirdly, interaction networks of lncRNA-nearby targeted mRNA and lncRNA-co-expressed mRNA were constructed in MF vs. AMI and HF vs. MF. Finally, expression validation and diagnostic capability analysis of selected lncRNAs and mRNAs were performed. Several lncRNA-co-expressed/nearby targeted mRNA pairs including AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 were identified. Several signaling pathways including TNF and cytokine-cytokine receptor interaction, fructose and mannose metabolism and HIF-1, hematopoietic cell lineage and fluid shear stress, and atherosclerosis and estrogen were selected. IL1R2, IRAK3, LRG1, and PLAC4 had a potential diagnostic value for both AMI and HF. Identified AC005392.3/AC007278.2-IL18R1, AL356356.1/AL137145.2-PFKFB3, and MKNK1-AS1/LINC01127-IL1R2 lncRNA-co-expressed/nearby targeted mRNA pairs may play crucial roles in the development of AMI, MF, and HF.

摘要

心肌梗死后心力衰竭(HF)的发病率和死亡率仍然居高不下。本研究的目的是在从急性心肌梗死(AMI)到心肌纤维化(MF)再到HF的进展过程中寻找潜在的长链非编码RNA(lncRNA)和信使核糖核酸(mRNA)。首先,采集AMI、MF和HF患者的血样进行RNA测序。其次,在MF与AMI以及HF与MF之间获得差异表达的lncRNA和mRNA,随后对两组之间共享的差异表达mRNA进行功能分析。第三,构建MF与AMI以及HF与MF之间lncRNA附近靶向mRNA和lncRNA共表达mRNA的相互作用网络。最后,对选定的lncRNA和mRNA进行表达验证和诊断能力分析。鉴定出了几对lncRNA共表达/附近靶向mRNA,包括AC005392.3/AC007278.2-IL18R1、AL356356.1/AL137145.2-PFKFB3以及MKNK1-AS1/LINC01127-IL1R2。选择了几条信号通路,包括肿瘤坏死因子(TNF)和细胞因子-细胞因子受体相互作用、果糖和甘露糖代谢以及低氧诱导因子-1(HIF-1)、造血细胞谱系和流体切应力,以及动脉粥样硬化和雌激素。白细胞介素1受体2(IL1R2)、白细胞介素1受体相关激酶3(IRAK3)、富含亮氨酸α2糖蛋白1(LRG1)和胎盘蛋白4(PLAC4)对AMI和HF均具有潜在诊断价值。鉴定出的AC005392.3/AC007278.2-IL18R1、AL356356.1/AL137145.2-PFKFB3以及MKNK1-AS1/LINC01127-IL1R2 lncRNA共表达/附近靶向mRNA对可能在AMI、MF和HF的发展中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2784/8322527/bdc45823c006/fcvm-08-664044-g0001.jpg

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