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Published on: June 15, 2018
Up-regulated lncRNA SNHG9 mediates the pathogenesis of dilated cardiomyopathy via miR-326/EPHB3 axis
Fan Zhang1,2, Hongtao Shi1, Honghong Xue2
1Department of Cardiology, the First Hospital of Shanxi Medical University, 85 South Jiefang Road, Taiyuan, Shanxi Province, 030001, People's Republic of China.
Insights
Serum SNHG9, a long non-coding RNA, acts as a promising biomarker for dilated cardiomyopathy (DCM). Its levels effectively distinguish DCM patients and correlate with heart function, suggesting a regulatory role in disease development.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biomarker Discovery
Background:
- Dilated cardiomyopathy (DCM) is a primary cause of heart failure and a leading reason for heart transplantation.
- Long non-coding RNAs (lncRNAs) are implicated in cardiac disease pathogenesis, but their specific roles in DCM remain unclear.
Purpose of the Study:
- To investigate the potential of serum lncRNAs as biomarkers for DCM.
- To identify specific lncRNAs, such as SNHG9, involved in DCM development and progression.
Main Methods:
- Re-analysis of GEO dataset (GSE124405) to identify aberrant plasma lncRNAs in heart failure patients.
- Utilized Receiver Operating Characteristic (ROC) curve analysis to evaluate the diagnostic performance of lncRNAs, including SNHG9.
- Assessed serum SNHG9 expression in a doxorubicin-induced DCM mouse model and evaluated the effect of SNHG9 deletion.
Main Results:
- Serum SNHG9 demonstrated significant diagnostic capability in distinguishing DCM from healthy controls and differentiating between DCM stages.
- Upregulated serum SNHG9 levels in a DCM mouse model were negatively correlated with cardiac function.
- AAV-9 mediated deletion of SNHG9 ameliorated cardiac injury in the doxorubicin-induced DCM model.
Conclusions:
- Serum SNHG9 is identified as a novel and valuable biomarker for dilated cardiomyopathy.
- SNHG9 plays a regulatory role in the development and progression of DCM.
- Targeting SNHG9 may offer a potential therapeutic strategy for DCM.
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.
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