Three miRNAs cooperate with host genes involved in human cardiovascular disease

Abstract

Background Understanding 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. Methods In 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. Results We 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. Conclusions Our work provides new insight into the regulatory network of the cardiovascular-associated pathways and opens the possibility for future experimental research. Electronic supplementary material The online version of this article (10.1186/s40246-019-0232-4) contains supplementary material, which is available to authorized users.

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“…The copyright holder for this this version posted December 2, 2020. ; https://doi.org/10.1101/2020.12.01.405910 doi: bioRxiv preprint 48 . The embedded miRNAs are often co-expressed with their host genes and can regulate their expression and activity 48,[59][60][61][62] , which support functional relations between the miRNA host-gene, target genes, and biological activity 63,64 . Indeed, we found that twelve of the identified dysregulated miRNAs were embedded in seven host genes that are known to be dysregulated in DMD models and patients (Supplemental table 7).…”

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