Comparative Expression of microRNAs in Young-Cardiomyocyte and hESC- Cardiomyocytes by bioinformatics methods

Introduction: Cardiac development is precisely controlled by complex regulatory networks. Recent reports demonstrated that microRNAs (miRNAs) act as micromanagers of gene expression at all stages of cardiac development. In this study, using different bioinformatics tools, we aimed to determine mRNAs and miRNAs expression profiles in human embryonic stem cell-derived cardiomyocytes (hESC-CMs). Methods: mRNAs and miRNAs were compared between 1-year matured hESC-CMs, and differentiated cardiomyocytes at day 20 (young-CM) samples of GSE62913. Then, differentially expressed mRNAs and miRNAs with padj<0.05 and log2FoldChange≠1 were chosen to perform pathway analysis. Pathway enrichment analysis and Regulatory Network were accomplished by Enrichr database and CytoscapeV3.6.0, respectively. In addition, miRWalk database was utilized to analyze the target genes of the highly expressed miRNAs.Results: Our data exhibited 2138 mRNAs and 172 miRNAs with different expression pattern. Pathway analysis and regulatory Network depicted that differentially expressed genes are involved in: complement and coagulation, cardiac progenitor differentiation, dilated cardiomyopathy, hypertrophic, and cardiac muscle contraction pathway. In the following, among differentially expressed miRNAs, hsa-miR-98-5p and hsa-miR-122-5p had the highest level of altered expression and were chosen for experimental validation. The upregulated hsa-miR-98-5p and downregulated hsa-miR-122-5p target the 3´-UTR of MTUS1 and FUNDC2 genes. The latter genes show high level of expression in artery and heart.Conclusion: All in all, cardiac development and cardiomyocyte maturity are very complicated. Determining the Cardiomyocyte-related miRNAs and their targets would shed more light on molecular processes of cardiac development.

Keywords:

Differentially expressed miRNAs , Young-Cardiomyocyte , hESC-CMs