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A CircRNA–miRNA–mRNA Network for Exploring Doxorubicin- and Myocet-Induced Cardiotoxicity in a Translational Porcine Model.
- Source :
- Biomolecules (2218-273X); Dec2023, Vol. 13 Issue 12, p1711, 16p
- Publication Year :
- 2023
-
Abstract
- Despite the widespread use of doxorubicin (DOX) as a chemotherapeutic agent, its severe cumulative cardiotoxicity represents a significant limitation. While the liposomal encapsulation of doxorubicin (Myocet, MYO) reduces cardiotoxicity, it is crucial to understand the molecular background of doxorubicin-induced cardiotoxicity. Here, we examined circular RNA expression in a translational model of pigs treated with either DOX or MYO and its potential impact on the global gene expression pattern in the myocardium. This study furthers our knowledge about the regulatory network of circRNA/miRNA/mRNA and its interaction with chemotherapeutics. Domestic pigs were treated with three cycles of anthracycline drugs (DOX, n = 5; MYO, n = 5) to induce cardiotoxicity. Untreated animals served as controls (control, n = 3). We applied a bulk mRNA-seq approach and the CIRIquant algorithm to identify circRNAs. The most differentially regulated circRNAs were validated under cell culture conditions, following forecasting of the circRNA–miRNA–mRNA network. We identified eight novel significantly regulated circRNAs from exonic and mitochondrial regions in the porcine myocardium. The forecasted circRNA–miRNA–mRNA network suggested candidate circRNAs that sponge miR-17, miR-15b, miR-130b, the let-7 family, and miR125, together with their mRNA targets. The identified circRNA–miRNA–mRNA network provides an updated, coherent view of the mechanisms involved in anthracycline-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]
- Subjects :
- CIRCULAR RNA
DOXORUBICIN
GENE expression
CARDIOTOXICITY
SWINE
CELL culture
MYOCARDIUM
Subjects
Details
- Language :
- English
- ISSN :
- 2218273X
- Volume :
- 13
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Biomolecules (2218-273X)
- Publication Type :
- Academic Journal
- Accession number :
- 174401714
- Full Text :
- https://doi.org/10.3390/biom13121711