A Specific Circulating MicroRNA Cluster Is Associated to Late Differential Cardiac Response to Doxorubicin-Induced Cardiotoxicity In Vivo.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_91107055CFF0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A Specific Circulating MicroRNA Cluster Is Associated to Late Differential Cardiac Response to Doxorubicin-Induced Cardiotoxicity In Vivo.
Journal
Disease markers
Author(s)
Ruggeri C., Gioffré S., Chiesa M., Buzzetti M., Milano G., Scopece A., Castiglioni L., Pontremoli M., Sironi L., Pompilio G., Colombo G.I., D'Alessandra Y.
ISSN
1875-8630 (Electronic)
ISSN-L
0278-0240
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
2018
Pages
8395651
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Cardiotoxicity is a detrimental side effect of the anticancer drug doxorubicin (DOX), characterized by progressive heart dysfunction. Circulating microRNAs (miRNAs) are recognized as potential biomarkers of cardiac disease; thus, we aimed to investigate their association with late cardiotoxicity in an animal model of disease.
Twenty C57BL/6 female mice were administered with 24 mg/kg cumulative dose of DOX or saline during 2 weeks, followed by a recovery period of one month (T42). Echocardiography was performed at baseline and at T42, and plasma samples were collected at T42. The selection of all miRNAs of interest was conducted by literature overview and by screening, followed by RT-qPCR validation. Results. The analysis of cardiac function at T42 evidenced five DOX-treated animals indistinguishable (NoTox) from controls (CTRLs), while four presented heart impairment (Tox). Our analyses identified eight dysfunction-associated plasma miRNAs. In particular, seven miRNAs were found downregulated in comparison to CTRLs, miR-1-3p, miR-122-5p, miR-127-3p, miR-133a-3p, miR-215-5p, miR-455-3-p, and miR-499a-5p. Conversely, miR-34a-5p showed increased levels in Tox plasma samples. Noteworthy, we determined a cluster composed of miR-1-3p, miR-34a-5p, miR-133a-3p, and miR-499a-5p that distinguished with high-accuracy Tox from NoTox mice.
This is the first study indicating that, similarly to what is observed in patients, DOX-administered animals present a differential cardiac response to treatment. Moreover, our results indicate the presence of specific plasma miRNAs whose expression reflect the presence of cardiac dysfunction in response to drug-induced injury.
Keywords
Animals, Cardiotoxicity/diagnostic imaging, Cardiotoxicity/genetics, Circulating MicroRNA/genetics, Disease Models, Animal, Doxorubicin/adverse effects, Echocardiography, Female, Genetic Markers, Humans, Mice, Mice, Inbred C57BL, MicroRNAs/genetics, Multigene Family
Pubmed
Web of science
Open Access
Yes
Create date
10/02/2019 15:36
Last modification date
20/08/2019 14:54
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