MicroRNAs (
miRNAs/miRs) 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. In the present study, high-throughput deep-sequencing was used to analyze changes in global
miRNA expression in H9c2 cardiomyocytes exposed to 5 µg/ml Dox for 0, 12 or 24 h. Compared with the 0-h time point, the expression levels of 386 unique
miRNAs were altered. Based on
miRNA expression and fold-change, the target genes of 76 selected
miRNAs were further analyzed using gene interaction networks and pathway enrichment analysis. These
miRNAs were involved in the regulation of different pathways, whose functions included apoptosis, cell proliferation, extracellular matrix 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 indicated that global wide
miRNA profiling in Dox-induced cardiomyocytes may provide a novel mechanistic insight into understanding Dox-induced
heart failure and
cardiotoxicity, as well as novel
biomarkers and therapeutic targets.