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

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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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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

DCM:

dilated cardiomyopathy

Dox:

doxorubicin

SNHG9:

small nucleolar RNA host gene 9

LncRNA:

long noncoding RNA

HF:

heart failure

HE:

hematoxylin-eosin

CHAST:

cardiac hypertrophy-associated transcript

LIPCAR:

the mitochondrial long noncoding RNA uc022bqs.1

AAV-9:

adeno-associated virus-9

LVEF:

left ventricular ejection fraction

LVFS:

left ventricular fractional shortening

LVIV:

LV internal volume

EPHB3:

Ephrin type-B receptor 3

FGF1:

fibroblast growth factor 1

PDE1B:

phosphodiesterase 1B

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81970204); National Natural Science Foundation of China (grant numbers 82100406); Research Project Supported by Shanxi Scholarship Council of China(grant numbers 2020-173); and the international cooperative scientific research foundation of Shanxi Science and Technology Department (grant numbers 201903D421024).

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Authors and Affiliations

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

    Fan zhang, Hongtao Shi, Hao Li & Qinghua Han

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

    Fan zhang, Honghong Xue & Chao Li

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  1. Fan zhang
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Contributions

Study design: QH. Experiments and data analysis: FZ, HX, HS, HL, CL. All contributed to the writing of the paper. All authors read and approved the final manuscript.

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Correspondence to Qinghua Han.

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All animal experimental procedures in this study were conducted in accordance with the guidelines of the animal ethical committee for animal experimentation, and the experimental design was approved by Shanxi Medical University.

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zhang, F., Shi, H., Xue, H. et al. Up-regulated lncRNA SNHG9 mediates the pathogenesis of dilated cardiomyopathy via miR-326/EPHB3 axis. J Thromb Thrombolysis 55, 634–648 (2023). https://doi.org/10.1007/s11239-023-02798-7

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