Noncoding RNA-Associated Competing Endogenous RNA Networks in Doxorubicin-Induced Cardiotoxicity

DNA Cell Biol. 2022 May 20. doi: 10.1089/dna.2022.0022. Online ahead of print.

Abstract

Accumulating evidence has indicated that noncoding RNAs (ncRNAs) are involved in doxorubicin-induced cardiotoxicity (DIC). However, the ncRNA-associated competing endogenous RNA (ceRNA)-mediated regulatory mechanisms in DIC remain unclear. In this study, we aimed to systematically investigate the alterations in expression levels of long noncoding RNA (lncRNA), circular RNA (circRNA), microRNA (miRNA), and mRNA in a DIC mouse model through deep RNA sequencing (RNA-seq). The results showed that 217 lncRNAs, 41 circRNAs, 11 miRNAs and 3633 mRNAs were aberrantly expressed. Moreover, the expression of 12 randomly selected transcripts was determined by real-time quantitative polymerase chain reaction to test the reliability of RNA-seq data. Based on the interaction between miRNAs and mRNAs, as well as lncRNAs/circRNAs and miRNAs, we constructed comprehensive lncRNA or circRNA-associated ceRNA networks in DIC mice. Moreover, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for differentially expressed genes. In conclusion, these identified ceRNA interactions provide new insight into the underlying mechanism and may be crucial therapeutic targets of DIC.

Keywords: RNA sequencing; cardiotoxicity; ceRNA network; doxorubicin; ncRNA.