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上调的长链非编码 RNA SNHG9 通过 miR-326/EPHB3 轴介导扩张型心肌病的发病机制。

Up-regulated lncRNA SNHG9 mediates the pathogenesis of dilated cardiomyopathy via miR-326/EPHB3 axis.

机构信息

Department of Cardiology, the First Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, Shanxi Province, 030001, People's Republic of China.

Shanxi Medical University, Taiyuan, 030001, Shanxi, China.

出版信息

J Thromb Thrombolysis. 2023 May;55(4):634-648. doi: 10.1007/s11239-023-02798-7. Epub 2023 Apr 1.

DOI:10.1007/s11239-023-02798-7
PMID:37004604
Abstract

Dilated cardiomyopathy (DCM) is a common cause of heart failure and also a major indication for heart transplantation. It has been reported that long non-coding RNAs (lncRNAs) are involved in the development of various cardiac diseases. However, the roles of lncRNAs in DCM are not fully understood. In this study, we uncovered that serum SNHG9 (small nucleolar RNA host gene 9, a lncRNA) serves as a biomarker for dilated cardiomyopathy. GEO datasets (GSE124405) were re-analyzed to identify the aberrant lncRNAs in the plasma sample of patients with heart failure. The receiver operating characteristic (ROC) curve was used to assess the expression alterations of the aberrant lncRNAs including SNHG9, XIST, PLCK2-AS1, KIF9-AS1, ARHGAP31-AS1, LINC00482, etc. Using the area under curve (AUC) of ROC, we found that serum SNHG9 exhibits considerable performance in distinguishing DCM from normal control and DCM stage-III from stage-I/II (New York Heart Association Class). Furthermore, we determined the serum SNHG9 expression level of the doxorubicin (Dox)-induced DCM mice model, and found that the upregulated SNHG9 is negatively associated with heart function. Besides, the deletion of SNHG9 by AAV-9 alleviated heart injury in the Dox-induced mice model. Taken together, the current results suggest that SNHG9 is a novel regulatory factor in dilated cardiomyopathy development.

摘要

扩张型心肌病(DCM)是心力衰竭的常见原因,也是心脏移植的主要指征。据报道,长链非编码 RNA(lncRNA)参与了各种心脏疾病的发生。然而,lncRNA 在 DCM 中的作用尚不完全清楚。在本研究中,我们发现血清 SNHG9(小核仁 RNA 宿主基因 9,一种 lncRNA)可作为扩张型心肌病的生物标志物。重新分析 GEO 数据集(GSE124405)以鉴定心力衰竭患者血浆样本中的异常 lncRNA。使用接收者操作特征(ROC)曲线评估异常 lncRNA 的表达变化,包括 SNHG9、XIST、PLCk2-AS1、KIF9-AS1、ARHGAP31-AS1、LINC00482 等。通过 ROC 的曲线下面积(AUC),我们发现血清 SNHG9 在区分 DCM 与正常对照以及 DCM Ⅲ期与Ⅰ/Ⅱ期(纽约心脏协会分级)方面具有相当的性能。此外,我们测定了阿霉素(Dox)诱导的 DCM 小鼠模型中的血清 SNHG9 表达水平,发现上调的 SNHG9 与心脏功能呈负相关。此外,AAV-9 介导的 SNHG9 缺失减轻了 Dox 诱导的小鼠模型中的心脏损伤。总之,目前的结果表明,SNHG9 是扩张型心肌病发展中的一种新型调节因子。

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