分析急性心肌梗死中不同表达的小鼠 miRNA 及与心率相关的靶基因

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Cell Biochemistry and Biophysics Pub Date : 2024-09-26 DOI:10.1007/s12013-024-01528-x
Zulikaier Tuerxun, Yuxin He, Yunxia Niu, Zhen Bao, Xuemei Liu, Yuchun Yang, Pengyi He
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引用次数: 0

摘要

研究目的本研究旨在探讨急性心肌梗死(AMI)后明显失调的 miRNAs 的表达谱及其潜在靶点:方法:建立急性心肌梗死小鼠模型后,从小鼠梗死心肌中提取 RNA。然后使用 Illumina NovaSeq 6000 系统进行配对端测序,以探索 miRNAs 的表达谱。利用 miRanda(3.3a 版)和 TargetScan(6.0 版)预测了下调差异表达 miRNA(DEmiRNA)的靶基因。使用 Cytoscape 构建 DEmiRNA-mRNA 调控网络,以显示调控关系。采用 RT-qPCR 技术检测 miR-142a-3p 在 H2O2 处理的大鼠心肌细胞 H9c2 细胞和 MI 大鼠心脏组织中的表达。通过细胞计数试剂盒-8和TUNEL检测H9c2细胞的活力和凋亡:结果:差异表达的 miRNA 有 33 个,其中 3 个显著上调,其余 30 个显著下调。通过基因本体(GO)分析,确定了这些 miRNA 的靶基因,并分析了它们的功能富集。重要的是,能调控心率的靶基因及其配对的上游 miRNA 引起了关注。研究发现,在小鼠心肌组织中,心率相关靶基因(Epas1、Bves、Hcn4、Cacna1e、Ank2、Slc8a1、Pde4d)与配对的 miRNA(miR-142a-5p、miR-7b-5p、miR-144-3p、miR-34c-5p、miR-223-3p、miR-18a-5p)之间存在显著的表达相关性。MiR-142a-3p在H9c2细胞和大鼠心梗组织中下调,过表达miR-142a-3p可抑制H2O2诱导的H9c2细胞凋亡:结论:在小鼠心肌组织中发现了miR-142a-3p等保护心脏的miRNA,一些特定的miRNA-靶标对与心率调节有关。
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Analysis of Differentially Expressed Murine miRNAs in Acute Myocardial Infarction and Target Genes Related to Heart Rate.

Objective: This study aims to investigate the expression profile of miRNAs significantly dysregulated after acute myocardial infarction (AMI) and their potential targets.

Methods: After the establishment of a mouse model of AMI, RNA was extracted from mouse infarcted myocardium. Paired-end sequencing was then performed using the Illumina NovaSeq 6000 system to explore the expression profile of miRNAs. Target genes of downregulated differentially expressed miRNAs (DEmiRNAs) were predicted with miRanda (version 3.3a) and TargetScan (version 6.0). Cytoscape was used to construct a DEmiRNA-mRNA regulatory network to show the regulatory relationship. RT-qPCR was performed to measure miR-142a-3p expression in H2O2-treated rat cardiomyocyte H9c2 cells and heart tissues of MI rats. Cell counting kit-8 and TUNEL assays were conducted to detect H9c2 cell viability and apoptosis.

Results: There were 33 differentially expressed miRNAs, of which 3 were significantly upregulated and the rest 30 were significantly downregulated. Target genes of these miRNAs were identified, and their functional enrichment was analyzed using gene ontology (GO) analysis. Importantly, target genes that can regulate heart rate and their paired upstream miRNAs attracted attention. Significant expression correlation between heart rate-related targets (Epas1, Bves, Hcn4, Cacna1e, Ank2, Slc8a1, Pde4d) and paired miRNAs (miR-142a-5p, miR-7b-5p, miR-144-3p, miR-34c-5p, miR-223-3p, miR-18a-5p) in mouse myocardial tissues was identified. MiR-142a-3p was downregulated in H9c2 cells and rat infarct tissues, and overexpressing miR-142a-3p restrains H2O2-induced H9c2 cell apoptosis.

Conclusion: Cardioprotective miRNAs, such as miR-142a-3p, were identified in mouse myocardial tissues, and some specific miRNA-target pairs are associated with heart rate regulation.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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