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

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

doi:10.1038/s41420-021-00687-7

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

Cell Death Discov. 2021 Oct 16;7(1):296. doi: 10.1038/s41420-021-00687-7.

Authors

Ziyi Bai^#¹, Haoran Sun^#¹, Xiuhong Li¹, Jie Wu², Hao Yuan¹, Guangde Zhang³, Haixiu Yang⁴, Hongbo Shi⁵

Affiliations

¹ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
² Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.
³ Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China. zhangguangde@ems.hrbmu.edu.cn.
⁴ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. yanghaixiu@ems.hrbmu.edu.cn.
⁵ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China. shihongbo@ems.hrbmu.edu.cn.

^# Contributed equally.

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.