| Description |
MicroRNAs (miRNAs) are sensitive biomarkers and endogenous repressors of gene expression by decreasing mRNA stability and interfering with mRNA translation. Despite a number of investigations revealing the dysregulation of miRNA expression associated with cardiotoxicity induced by doxorubicin (Dox), perturbation of miRNAs directly resulting from Dox at early stage in cardiomyocytes and the target gene interaction remain largely unknown. The high-throughput deep-sequencing was used to analyze changes in global microRNA expression in cardiomyocytes, H9c2 cells, exposed to 5 μg/ml Dox for 0, 12 or 24 h, respectively. Compared with the 0-h time point, expression levels of 386 unique miRNAs were altered. Based on expression level and fold-change in miRNAs, target genes of 76 selected miRNAs were further analyzed with gene interaction networks and pathway enrichment. These miRNAs are involved in the regulation of different pathways, whose functions include cell apoptosis, proliferation, extracellular matrix (ECM) remodeling, oxidative stress and lipid metabolism. These differentially expressed miRNAs included let-7 family, miR-29b-3p, miR-378-3/5p, miR-351-3p, miR-664-3p, miR-455-3p, miR-298-3p, miR-702-5p, miR-128-1-5p, miR-671 and miR-421-5p. The present data showed that global wide miRNA profiling in Dox-induced cardiomyocytes could provide a novel mechanistic insight into understanding Dox-induced heart failure and cardiotoxicity, as well as new biomarkers and therapeutic targets. |
