Doxorubicin (DOX)-induced
cardiotoxicity impedes its clinical application, but the mechanisms have not been thoroughly elucidated. Based on
circRNA and
mRNA expression profiles, we illustrated
RNA expression signature changes during DOX-induced
cardiotoxicity; mechanism exploration and
biomarkers screening were also conducted. Twelve mice were randomly divided into two groups, induction group was treated with
doxorubicin, and the control group was given an equal quantity of saline. After the confirmation of myocardial injury in induction group, the heart tissues from both groups were isolated for
RNA high-throughput sequencing. The expression profiles were compared between the two groups; a total of 295 mRNAs and 11
circRNAs were shown as biased expression in DOX-induced
cardiotoxicity mouse hearts. The dysregulation of three
circRNAs were validated by quantitative real-time PCR: mmu_circ_0015773, mmu_circ_0002106, and mmu_circ_001606. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the differentially expressed RNAs were performed; the results implied that DOX might cause
cardiotoxicity by interfering
hemoglobin-based
oxygen delivery and
DNA-associated signal pathways. We integrated the differential expressed
mRNA and validated
circRNAs by constructing a
competing endogenous RNA (
ceRNA) network, which indicated that the alteration of the three
circRNAs could activate apoptosis process of myocardial cells. This study provided novel insight into the mechanisms of DOX induced
cardiotoxicity, and potential
biomarkers or therapeutic targets were also proposed.