Three miRNAs cooperate with host genes involved in human cardiovascular disease

Yan Zhu,Jingjing Xie,Hong Sun

doi:10.1186/s40246-019-0232-4

Yan Zhu, Jingjing Xie + Show 1 more

Open Access

https://doi.org/10.1186/s40246-019-0232-4

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Abstract

BackgroundUnderstanding the roles of miRNAs in cardiovascular disease remains a challenge. Genomic linkage indicates a functional relationship between intronic miRNAs and their host genes. However, few studies have shown functional association between intronic miRNAs and their host coding genes that are genetically associated with cardiovascular disease.MethodsIn this study, we investigated functional relationship between three protein-coding genes genetically associated with cardiovascular disease, i.e., CDH13, SLC12A3, and CKAP5, and their intronic miRNAs using a data-driven approach.ResultsWe found that the three protein-coding genes functionally interact with targets of their intronic miRNAs, i.e., miR-3182, miR-6863, and miR-5582, in a tissue-specific pattern. The intronic miRNAs preferentially impact important genes for the three host genes in the network, indicating their roles in maintaining the integrity of the interactome where the host genes are involved. Targets of the intronic miRNAs display functional similarity to the host genes. We furthermore present sets of target genes for future investigation on the possible miRNA-target interactions that potentially contribute to cardiovascular diseases.ConclusionsOur work provides new insight into the regulatory network of the cardiovascular-associated pathways and opens the possibility for future experimental research.

Highlights

The connection between miRNAs and disease was demonstrated to be obvious [1,2,3,4]. miRNAs have been implicated in a wide variety of cardiovascular disorder, including heart failure, cardiac hypertrophy, remodeling after myocardial infarction, arrhythmias, atherosclerosis, atrial fibrillation, and peripheral artery disease [5, 6]
As disordered interplays between genes in tissue-specific processes were frequently found in human diseases [17, 18], in this work, we investigated the functional relationship between three genes, which are genetically associated with cardiovascular disease (CVD), and their intronic miRNAs with a data-driven approach based on a large-scale tissue-specific gene interaction data [11] and gene annotation data
Among the set of protein-coding genes genetically related to CVD, we found three genes colocalize with miRNA, that is, CDH13 hosts miR-3182 (Additional file 1: Figure S2), SLC12A3 hosts miR-6863 (Additional file 1: Figure S3), and CKAP5 hosts miR5582 (Additional file 1: Figure S4)

Summary

Introduction

The connection between miRNAs and disease was demonstrated to be obvious [1,2,3,4]. miRNAs have been implicated in a wide variety of cardiovascular disorder, including heart failure, cardiac hypertrophy, remodeling after myocardial infarction, arrhythmias, atherosclerosis, atrial fibrillation, and peripheral artery disease [5, 6]. Studies have shown that miRNAs play important roles in cardiac signaling and transcriptional pathways and that they act as “rheostats” and “switches” to modulate various aspects of cardiac development [7, 8]. Functions in cardiac-associated pathways for some miRNAs have been verified, e.g., MiR-18a-5p inhibits endothelial-mesenchymal transition and cardiac fibrosis through the Notch pathway [7], and some miRNAs act as Characterizing the influence of miRNAs in the context of targets is critical to better understand how miRNAs influence disease processes. Understanding the roles of miRNAs in cardiovascular disease remains a challenge. Genomic linkage indicates a functional relationship between intronic miRNAs and their host genes. Few studies have shown functional association between intronic miRNAs and their host coding genes that are genetically associated with cardiovascular disease

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Conclusion