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...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1055911/full |
| _version_ | 1797984021034041344 |
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| author | Ippei Kawano Michaela Adamcova |
| author_facet | Ippei Kawano Michaela Adamcova |
| author_sort | Ippei Kawano |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:56:11Z |
| format | Article |
| id | doaj.art-ed25ab781e8745cdae0cd17976d7244f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T06:56:11Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ed25ab781e8745cdae0cd17976d7244f2022-12-22T04:39:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-11-011310.3389/fphar.2022.10559111055911MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage responseIppei KawanoMichaela AdamcovaDoxorubicin (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.https://www.frontiersin.org/articles/10.3389/fphar.2022.1055911/fullmicroRNAdoxorubicincardiotoxicitygenotoxic stressp53 |
| spellingShingle | Ippei Kawano Michaela Adamcova MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response Frontiers in Pharmacology microRNA doxorubicin cardiotoxicity genotoxic stress p53 |
| title | MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response |
| title_full | MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response |
| title_fullStr | MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response |
| title_full_unstemmed | MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response |
| title_short | MicroRNAs in doxorubicin-induced cardiotoxicity: The DNA damage response |
| title_sort | micrornas in doxorubicin induced cardiotoxicity the dna damage response |
| topic | microRNA doxorubicin cardiotoxicity genotoxic stress p53 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1055911/full |
| work_keys_str_mv | AT ippeikawano micrornasindoxorubicininducedcardiotoxicitythednadamageresponse AT michaelaadamcova micrornasindoxorubicininducedcardiotoxicitythednadamageresponse |