MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response

Doxorubicin (DOX) is a chemotherapeutic drug widely used for cancer treatment, but its use is limited by cardiotoxicity. Although free radicals from redox cycling and free cellular iron have been predominant as the suggested primary pathogenic mechanism, novel evidence has pointed to topoisomerase I...

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Bibliographic Details
Published in:Frontiers in pharmacology 2022-11, Vol.13, p.1055911-1055911
Main Authors: Kawano, Ippei, Adamcova, Michaela
Format: Article
Language:English
Subjects:
cardiotoxicity
doxorubicin
genotoxic stress
microRNA
p53
Pharmacology
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Summary:Doxorubicin (DOX) is a chemotherapeutic drug widely used for cancer treatment, but its use is limited by cardiotoxicity. Although free radicals from redox cycling and free cellular iron have been predominant as the suggested primary pathogenic mechanism, novel evidence has pointed to topoisomerase II inhibition and resultant genotoxic stress as the more fundamental mechanism. Recently, a growing list of microRNAs (miRNAs) has been implicated in DOX-induced cardiotoxicity (DIC). This review summarizes miRNAs reported in the recent literature in the context of DIC. A particular focus is given to miRNAs that regulate cellular responses downstream to DOX-induced DNA damage, especially p53 activation, pro-survival signaling pathway inhibition (e.g., AMPK, AKT, GATA-4, and sirtuin pathways), mitochondrial dysfunction, and ferroptosis. Since these pathways are potential targets for cardioprotection against DOX, an understanding of how miRNAs participate is necessary for developing future therapies.
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2022.1055911