Integrative analysis of competing endogenous RNA networks reveals the functional lncRNAs in heart failure

Abstract

Heart failure has become one of the top causes of death worldwide. It is increasing evidence that lncRNAs play important roles in the pathology processes of multiple cardiovascular diseases. Additionally, lncRNAs can function as ceRNAs by sponging miRNAs to affect the expression level of mRNAs, implicating in numerous biological processes. However, the functional roles and regulatory mechanisms of lncRNAs in heart failure are still unclear. In our study, we constructed a heart failure‐related lncRNA‐mRNA network by integrating probe re‐annotation pipeline and miRNA‐target interactions. Firstly, some lncRNAs that had the central topological features were found in the heart failure‐related lncRNA‐mRNA network. Then, the lncRNA‐associated functional modules were identified from the network, using bidirectional hierarchical clustering. Some lncRNAs that involved in modules were demonstrated to be enriched in many heart failure‐related pathways. To investigate the role of lncRNA‐associated ceRNA crosstalks in certain disease or physiological status, we further identified the lncRNA‐associated dysregulated ceRNA interactions. And we also performed a random walk algorithm to identify more heart failure‐related lncRNAs. All these lncRNAs were verified to show a strong diagnosis power for heart failure. These results will help us to understand the mechanism of lncRNAs in heart failure and provide novel lncRNAs as candidate diagnostic biomarkers or potential therapeutic targets.

Identification of functional lncRNAs in atrial fibrillation by integrative analysis of the lncRNA‐mRNA network based on competing endogenous RNAs hypothesis

“…Emerging studies have suggested that ceRNAs exerted functions in certain disease or normal status (Shao et al, ). For example, Fan et al () constructed dysregulated ceRNA networks for heart failure and physiological condition and identified some key lncRNAs in the networks. Paci, Colombo, and Farina () built networks of miRNA‐mediated sponge interactions for healthy controls and breast cancer, which highlighted a marked rewiring in the ceRNA program between normal and disease status.…”

Competing Endogenous RNAs, Non-Coding RNAs and Diseases: An Intertwined Story

“…Some ncRNAs-miRNAs-mRNAs networks were analyzed, leading to the discovery of numerous lncRNAs functional modules in heart failure [ 94 ] and in cardiac hypertrophy (CH), involving important oncogenic and well-characterized disease-related lncRNAs, such as HOX transcript antisense intergenic RNA (HOTAIR) [ 95 ] or myocardial infarction and associated transcript (MIAT) [ 96 , 97 ]. Specifically in CH, the crucial role of three new characterized lncRNAs (SLC26A4-AS1, RP11-344E13.3 and MAGI1-IT) was proven [ 98 ] by combining miRNA-transcript interactions, expression data of cardiac hypertrophy from an expressly re-annotated gene expression dataset, publicly available on Gene Expression Omnibus (GEO, a public functional genomics data repository), and an analysis of the most important network topological features like the degree, betweenness and closeness.…”

Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture

“…Manipulation of the expression of the Wisper, Meg3, and MIAT lncRNAs also affects cardiac fibrosis and pathological remodeling 47 – 49 . Tissue and plasma lncRNAs have been identified as potential biomarkers to predict the disease outcome for heart failure 32 , 50 – 52 . These studies highlight the therapeutic potential for lncRNA-targeted treatment for heart failure.…”