Time-ordered dysregulated ceRNA networks reveal disease progression and diagnostic biomarkers in ischemic and dilated cardiomyopathy

Ziyi Bai,Xiuhong Li,Hao Yuan,Haixiu Yang,Haoran Sun,Hongbo Shi,Jie Wu,Guangde Zhang

doi:10.1038/s41420-021-00687-7

Abstract

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two main causes of heart failure (HF). Despite similar clinical characteristics and common “HF pathways”, ICM and DCM are expected to have different personalized treatment strategies. The underlying mechanisms of ICM and DCM have yet to be fully elucidated. The present study developed a novel computational method for identifying dysregulated long noncoding RNA (lncRNA)–microRNA (miRNA)–mRNA competing endogenous RNA (ceRNA) triplets. Time-ordered dysregulated ceRNA networks were subsequently constructed to reveal the possible disease progression of ICM and DCM based on the method. Biological functional analysis indicated that ICM and DCM had similar features during myocardial remodeling, whereas their characteristics differed during progression. Specifically, disturbance of myocardial energy metabolism may be the main characteristic during DCM progression, whereas early inflammation and response to oxygen are the characteristics that may be specific to ICM. In addition, several panels of diagnostic biomarkers for differentiating non-heart failure (NF) and ICM (NF-ICM), NF-DCM, and ICM-DCM were identified. Our study reveals biological differences during ICM and DCM progression and provides potential diagnostic biomarkers for ICM and DCM.

Highlights

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two most commonly occurring etiologies for heart failure (HF)
1271 dysregulated LMMCTs including 97 long noncoding RNA (lncRNA), 85 miRNAs, and 675 mRNAs in ICM were obtained, and 1298 dysregulated lncRNA-miRNA-mRNA ceRNA triplets (LMM-CTs) consisting of 107 lncRNAs, 96 miRNAs, and 727 mRNAs in DCM were identified (Supplementary Table S1)
The results showed that the proportions of significantly differentially expressed (SDE) genes and DisGenes in dysregulated LMM-CTs were both significantly higher than that of non-heart failure (NF) LMM-CTs

Summary

Introduction

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two most commonly occurring etiologies for heart failure (HF). Due to strong similarities between the two diseases, the clinical differentiation between ICM and DCM currently depends mainly on the results of coronary angiography, a procedure that is both invasive and expensive [2]. Great effort is being made to investigate common HF pathways and disease-specific characteristics in ICM and DCM [3,4,5,6,7,8,9,10,11]. At the proteome and metabolome levels, gender-specific pathways in ICM and DCM have been unveiled in myocardial samples [10]. Commonalities of HF pathways and disease-specific metabolic features were founded through the analysis of plasma samples, and metabolite biomarkers for differentiating patients with ICM and DCM were identified [11]. The underlying biological mechanisms of ICM and DCM contributing to HF have yet to be fully elucidated, and the above-mentioned studies were all performed at the single molecular level, ignoring the interactions among molecules

Methods

Results

Conclusion