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

Ziyi Bai1, Haoran Sun1, Xiuhong Li1

  • 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Cell Death Discovery
|October 17, 2021
PubMed

Insights

This study identifies distinct molecular pathways in ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) progression using a novel computational method. Findings reveal unique biological characteristics for each condition, aiding in personalized heart failure treatment.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Computational Biology

Background:

  • Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are leading causes of heart failure (HF).
  • Despite shared HF pathways, distinct mechanisms necessitate personalized treatment strategies.
  • The underlying molecular mechanisms of ICM and DCM remain incompletely understood.

Purpose of the Study:

  • To develop a computational method for identifying dysregulated long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA competing endogenous RNA (ceRNA) triplets.
  • To construct time-ordered ceRNA networks to elucidate disease progression in ICM and DCM.
  • To identify potential diagnostic biomarkers for differentiating heart failure subtypes.

Main Methods:

  • Novel computational method for identifying dysregulated lncRNA-miRNA-mRNA ceRNA triplets.
  • Construction of time-ordered dysregulated ceRNA networks.
  • Biological functional analysis and biomarker panel identification.

Main Results:

  • ICM and DCM share features during myocardial remodeling but diverge during progression.
  • DCM progression is characterized by disturbed myocardial energy metabolism.
  • ICM progression involves early inflammation and oxygen response.
  • Diagnostic biomarker panels for non-heart failure (NF), ICM, and DCM were identified.

Conclusions:

  • Distinct biological progression pathways exist for ICM and DCM.
  • Computational identification of ceRNA networks provides insights into HF mechanisms.
  • Identified biomarkers may aid in differentiating ICM and DCM, guiding personalized treatment.

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