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In Vivo Nanovector Delivery of a Heart-specific MicroRNA-sponge
Published on: June 15, 2018
MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity
Gustav Holmgren1, Jane Synnergren2, Christian X Andersson3
1Systems Biology Research Center, School of Bioscience, University of Skövde, Box 408 Kanikegränd 3A, SE-541 28, Skövde, Sweden; Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45, Gothenburg, Sweden.
Abstract:
Anthracyclines, such as doxorubicin, are well-established, highly efficient anti-neoplastic drugs used for treatment of a variety of cancers, including solid tumors, leukemia, lymphomas, and breast cancer. The successful use of doxorubicin has, however, been hampered by severe cardiotoxic side-effects. In order to prevent or reverse negative side-effects of doxorubicin, it is important to find early biomarkers of heart injury and drug-induced cardiotoxicity. The high stability under extreme conditions, presence in various body fluids, and tissue-specificity, makes microRNAs very suitable as clinical biomarkers. The present study aimed towards evaluating the early and late effects of doxorubicin on the microRNA expression in cardiomyocytes derived from human pluripotent stem cells. We report on several microRNAs, including miR-34a, miR-34b, miR-187, miR-199a, miR-199b, miR-146a, miR-15b, miR-130a, miR-214, and miR-424, that are differentially expressed upon, and after, treatment with doxorubicin. Investigation of the biological relevance of the identified microRNAs revealed connections to cardiomyocyte function and cardiotoxicity, thus supporting the findings of these microRNAs as potential biomarkers for drug-induced cardiotoxicity.
Insights
Doxorubicin is an effective cancer drug, but can harm the heart. This study identifies specific microRNAs as potential early biomarkers for detecting doxorubicin-induced cardiotoxicity in heart cells.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Anthracyclines like doxorubicin are vital anti-cancer drugs.
- Doxorubicin treatment can cause severe cardiotoxicity, limiting its clinical use.
- Early detection of cardiotoxicity is crucial for patient management.
Purpose of the Study:
- To investigate the impact of doxorubicin on microRNA expression in human cardiomyocytes.
- To identify potential microRNA biomarkers for early detection of drug-induced cardiotoxicity.
Main Methods:
- Human pluripotent stem cell-derived cardiomyocytes were treated with doxorubicin.
- MicroRNA expression profiling was performed to analyze changes.
- Bioinformatic analysis was used to assess the biological relevance of identified microRNAs.
Main Results:
- Doxorubicin treatment led to differential expression of several microRNAs (e.g., miR-34a, miR-146a, miR-214).
- The identified microRNAs are linked to cardiomyocyte function and cardiotoxicity pathways.
- Specific microRNAs showed altered expression both during and after doxorubicin exposure.
Conclusions:
- MicroRNAs are promising candidates for early biomarkers of doxorubicin-induced cardiotoxicity.
- Monitoring these microRNAs could aid in preventing or managing heart damage from cancer therapy.
- This research provides a foundation for developing novel diagnostic tools for cardiotoxicity.

