Expression changes and clinical significance of miR⁃5196⁃5p and miR⁃652⁃5p in dilated cardiomyopathy patients
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摘要:
目的：通过miRNA Array芯片技术，了解扩张型心肌病（dilated cardiomyopathy，DCM）患者血浆miRNA表达谱的差异，探索这种差异与左室舒张末内径（left ventricular end-diastolic dimension，LVEDd）、左室射血分数（left ventricular ejection fraction，LVEF）及N末端脑钠肽前体（N-terminal of the prohormone brain natriuretic peptide，NT-proBNP）等心衰指标的关系，并预测其作用靶基因。方法：入选南京胸科医院心脏科收住的8例明确诊断的DCM患者，抽提血浆总RNA，采用Agilent Human miRNAs Array（V19.0）芯片技术，与4例健康对照进行表达谱的差异筛选，对改变最明显的miRNA进行30例患者的进一步验证。检测两组受检者生化指标、NT-proBNP，测量LVEDd、LVEF，并进行变量间的相关分析。TargetScan和miRBD数据库预测靶基因。结果：与对照组相比，病例组中共发现36个有意义的miRNAs表达差异，其中25个上调的miRNA中，miR-5196-5p上调最明显，下调的miRNA中，miR-652-5p下调最明显。该结果在后续30例DCM患者的验证中也得到证实。Pearson线性相关分析显示，miR-5196-5p上调水平与LVEDd呈正相关，miR-652-5p水平与LVEDd、NT-proBNP呈负相关，与LVEF呈正相关。靶基因分别预测到DCM相关基因VCL、RBM20等。结论：DCM患者血浆中miR-5196-5p表达明显上调，miR-652-5p表达下调，并与左室功能、心室重构相关。进一步研究有可能揭示miR-5196-5p、miR-652-5p在心衰致病中的机制，并有可能成为评估疾病疗效及预后的新指标或潜在治疗靶点。
Abstract:
Objective：The study aimed to investigate differentially expressed microRNAs（miRNAs）and their association with left ventricular end-diastolic dimension（LVEDd），left ventricular ejection fraction（LVEF），N-terminal of the prohormone brain natriuretic peptide（NT-proBNP）in human dilated cardiomyopathy（DCM）by miRNAs array，and to predict their target gene. Methods：The expression levels of plasma miRNAs of 8 DCM patients and 4 healthy controls were detected by using the Agilent human miRNAs array（V19.0），followed by real-time RT-PCR analysis to validate the expression changes of miRNAs. NT-proBNP，LVEDd and LVEF were measured and analyzed using Pearson linear correlation analysis. The prediction analysis for microarrays（PAM）method was used to identify the differentially expressed miRNAs. Results：Thirty-six differentially expressed miRNAs were identified. There were 25 upregulated and 11 downregulated human miRNAs，of which miR-5196-5p and miR-652-5p were the most significant. Pearson linear correlation analysis showed that miR-5196-5p level was positively correlated with LVEDd，whereas miR-652-5p was positively correlated with LVEF values and negatively correlated with NT-proBNP and LVEDd. Moreover，correlative genes such as VCL and RBM20 related with DCM were predicted. Conclusion：The screened differentially expressed miRNAs may be involved in the development of DCM. Specific miRNAs，such as miR-5196-5p and miR-652-5p，may be considered as new targets for the diagnosis and treatment of human DCM.
