Skip to main content
SpringerLink
Log in

The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity

  • Cardio-Oncology
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Cardiovascular disease is the main factor contributing to the global burden of diseases, and the cardiotoxicity caused by anticancer drugs is an essential component that cannot be ignored. With the development of anticancer drugs, the survival period of cancer patients is prolonged; however, the cardiotoxicity caused by anticancer drugs is becoming increasingly prominent. Currently, cardiovascular disease has emerged as the second leading cause of mortality among long-term cancer survivors. Anticancer drug-induced cardiotoxicity has become a frontier and hot topic. The discovery of epigenetics has given the possibility of environmental changes in gene expression, protein synthesis, and traits. It has been found that epigenetics plays a pivotal role in promoting cardiovascular diseases, such as heart failure, coronary heart disease, and hypertension. In recent years, increasing studies have underscored the crucial roles played by epigenetics in anticancer drug-induced cardiotoxicity. Here, we provide a comprehensive overview of the role and mechanisms of epigenetics in anticancer drug-induced cardiotoxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. An Y, Duan H (2022) The role of m6A RNA methylation in cancer metabolism. Mol Cancer 21:14. https://doi.org/10.1186/s12943-022-01500-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ashrafizaveh S, Ashrafizadeh M, Zarrabi A, Husmandi K, Zabolian A, Shahinozzaman M, Aref AR, Hamblin MR, Nabavi N, Crea F, Wang Y, Ahn KS (2021) Long non-coding RNAs in the doxorubicin resistance of cancer cells. Cancer Lett 508:104–114. https://doi.org/10.1016/j.canlet.2021.03.018

    Article  CAS  PubMed  Google Scholar 

  3. Aung LHH, Chen X, Cueva Jumbo JC, Li Z, Wang SY, Zhao C, Liu Z, Wang Y, Li P (2021) Cardiomyocyte mitochondrial dynamic-related lncRNA 1 (CMDL-1) may serve as a potential therapeutic target in doxorubicin cardiotoxicity. Mol Ther Nucleic Acids 25:638–651. https://doi.org/10.1016/j.omtn.2021.08.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Backs J, Olson EN (2006) Control of cardiac growth by histone acetylation/deacetylation. Circ Res 98:15–24. https://doi.org/10.1161/01.RES.0000197782.21444.8f

    Article  CAS  PubMed  Google Scholar 

  5. Bertheloot D, Latz E, Franklin BS (2021) Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol 18:1106–1121. https://doi.org/10.1038/s41423-020-00630-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Berulava T, Buchholz E, Elerdashvili V, Pena T, Islam MR, Lbik D, Mohamed BA, Renner A, von Lewinski D, Sacherer M, Bohnsack KE, Bohnsack MT, Jain G, Capece V, Cleve N, Burkhardt S, Hasenfuss G, Fischer A, Toischer K (2020) Changes in m6A RNA methylation contribute to heart failure progression by modulating translation. Eur J Heart Fail 22:54–66. https://doi.org/10.1002/ejhf.1672

    Article  CAS  PubMed  Google Scholar 

  7. Boovarahan SR, Kurian GA (2021) Preconditioning the rat heart with 5-azacytidine attenuates myocardial ischemia/reperfusion injury via PI3K/GSK3beta and mitochondrial KATP signaling axis. J Biochem Mol Toxicol 35:e22911. https://doi.org/10.1002/jbt.22911

    Article  CAS  PubMed  Google Scholar 

  8. Braile M, Marcella S, Cristinziano L, Galdiero MR, Modestino L, Ferrara AL, Varricchi G, Marone G, Loffredo S (2020) VEGF-A in cardiomyocytes and heart diseases. Int J Mol Sci 21:5294. https://doi.org/10.3390/ijms21155294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bravo-San Pedro JM, Kroemer G, Galluzzi L (2017) Autophagy and mitophagy in cardiovascular disease. Circ Res 120:1812–1824. https://doi.org/10.1161/circresaha.117.311082

    Article  CAS  PubMed  Google Scholar 

  10. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM (2010) Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol 55:213–220. https://doi.org/10.1016/j.jacc.2009.03.095

    Article  CAS  PubMed  Google Scholar 

  11. Chen L, Yan K-P, Liu X-C, Wang W, Li C, Li M, Qiu C-G (2017) Valsartan regulates TGF-β/Smads and TGF-β/p38 pathways through lncRNA CHRF to improve doxorubicin-induced heart failure. Arch Pharmacal Res 41:101–109. https://doi.org/10.1007/s12272-017-0980-4

    Article  CAS  Google Scholar 

  12. Chen S, Wang J, Zhou Y (2019) Long non-coding RNA SNHG1 protects human AC16 cardiomyocytes from doxorubicin toxicity by regulating miR-195/Bcl-2 axis. Biosci Rep 39:BSR20191050. https://doi.org/10.1042/BSR20191050

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen XY, Huang WL, Peng XP, Lv YN, Li JH, Xiong JP (2019) miR-140-5p mediates bevacizumab-induced cytotoxicity to cardiomyocytes by targeting the VEGFA/14-3-3γ signal pathway. Toxicol Res (Cambr) 8:875–884. https://doi.org/10.1039/c9tx00100j

    Article  CAS  Google Scholar 

  14. Daosukho C, Chen Y, Noel T, Sompol P, Nithipongvanitch R, Velez JM, Oberley TD, Clair DK (2007) Phenylbutyrate, a histone deacetylase inhibitor, protects against Adriamycin-induced cardiac injury. Free Radic Biol Med 42:1818–1825. https://doi.org/10.1016/j.freeradbiomed.2007.03.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Christidi E, Brunham LR (2021) Regulated cell death pathways in doxorubicin-induced cardiotoxicity. Cell Death Dis 12:339. https://doi.org/10.1038/s41419-021-03614-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cooper SL, Sandhu H, Hussain A, Mee C, Maddock H (2018) Involvement of mitogen activated kinase kinase 7 intracellular signalling pathway in Sunitinib-induced cardiotoxicity. Toxicology 394:72–83. https://doi.org/10.1016/j.tox.2017.12.005

    Article  CAS  PubMed  Google Scholar 

  17. Cui L, Guo J, Zhang Q, Yin J, Li J, Zhou W, Zhang T, Yuan H, Zhao J, Zhang L, Carmichael PL, Peng S (2017) Erythropoietin activates SIRT1 to protect human cardiomyocytes against doxorubicin-induced mitochondrial dysfunction and toxicity. Toxicol Lett 275:28–38. https://doi.org/10.1016/j.toxlet.2017.04.018

    Article  CAS  PubMed  Google Scholar 

  18. Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, Cipolla CM (2016) Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin 66:309–325. https://doi.org/10.3322/caac.21341

    Article  PubMed  Google Scholar 

  19. de Baat EC, Mulder RL, Armenian S, Feijen EA, Grotenhuis H, Hudson MM, Mavinkurve-Groothuis AM, Kremer LC, van Dalen EC (2022) Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines. Cochrane Database Syst Rev 9:Cd014638. https://doi.org/10.1002/14651858.CD014638.pub2

    Article  PubMed  Google Scholar 

  20. Deng Z, Yao J, Xiao N, Han Y, Wu X, Ci C, Chen K, Geng X (2022) DNA methyltransferase 1 (DNMT1) suppresses mitophagy and aggravates heart failure via the microRNA-152-3p/ETS1/RhoH axis. Lab Investig 102:782–793. https://doi.org/10.1038/s41374-022-00740-8

    Article  CAS  PubMed  Google Scholar 

  21. Devaux Y, Nossent AY, CA EU-CCA (2020) A role for m6A RNA methylation in heart failure development? Eur J Heart Fail 22:67–69. https://doi.org/10.1002/ejhf.1714

    Article  PubMed  Google Scholar 

  22. Donate Puertas R, Meugnier E, Romestaing C, Rey C, Morel E, Lachuer J, Gadot N, Scridon A, Julien C, Tronc F, Chapuis B, Valla C, Janin A, Pirola L, Mejat A, Rome S, Chevalier P (2017) Atrial fibrillation is associated with hypermethylation in human left atrium, and treatment with decitabine reduces atrial tachyarrhythmias in spontaneously hypertensive rats. Transl Res 184(57–67):e5. https://doi.org/10.1016/j.trsl.2017.03.004

    Article  CAS  Google Scholar 

  23. El Kiki SM, Omran MM, Mansour HH, Hasan HF (2020) Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats. Mol Biol Rep 47:5115–5126. https://doi.org/10.1007/s11033-020-05582-5

    Article  CAS  PubMed  Google Scholar 

  24. Elrashidy RA, Hasan RA (2021) Cilostazol preconditioning alleviates cyclophosphamide-induced cardiotoxicity in male rats: mechanistic insights into SIRT1 signaling pathway. Life Sci 266:118822. https://doi.org/10.1016/j.lfs.2020.118822

    Article  CAS  PubMed  Google Scholar 

  25. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12:861–874. https://doi.org/10.1038/nrg3074

    Article  CAS  PubMed  Google Scholar 

  26. Ewer MS, Ewer SM (2010) Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol 7:564–575. https://doi.org/10.1038/nrcardio.2010.121

    Article  PubMed  Google Scholar 

  27. Ferreira LL, Cervantes M, Froufe HJC, Egas C, Cunha-Oliveira T, Sassone-Corsi P, Oliveira PJ (2020) Doxorubicin persistently rewires cardiac circadian homeostasis in mice. Arch Toxicol 94:257–271. https://doi.org/10.1007/s00204-019-02626-z

    Article  CAS  PubMed  Google Scholar 

  28. Ferreira LL, Cunha-Oliveira T, Veloso CD, Costa CF, Wallace KB, Oliveira PJ (2019) Single nanomolar doxorubicin exposure triggers compensatory mitochondrial responses in H9c2 cardiomyoblasts. Food Chem Toxicol 124:450–461. https://doi.org/10.1016/j.fct.2018.12.017

    Article  CAS  PubMed  Google Scholar 

  29. Gilchrist SC, Barac A, Ades PA, Alfano CM, Franklin BA, Jones LW, La Gerche A, Ligibel JA, Lopez G, Madan K, Oeffinger KC, Salamone J, Scott JM, Squires RW, Thomas RJ, Treat-Jacobson DJ, Wright JS, American Heart Association Exercise CR, Secondary Prevention Committee of the Council on Clinical C, Council on C, Stroke N, Council on Peripheral Vascular D (2019) Cardio-oncology rehabilitation to manage cardiovascular outcomes in cancer patients and survivors: a scientific statement from the American Heart Association. Circulation 139:e997–e1012. https://doi.org/10.1161/CIR.0000000000000679

    Article  PubMed  PubMed Central  Google Scholar 

  30. Giordano FJ, Gerber HP, Williams SP, VanBruggen N, Bunting S, Ruiz-Lozano P, Gu Y, Nath AK, Huang Y, Hickey R, Dalton N, Peterson KL, Ross J Jr, Chien KR, Ferrara N (2001) A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 98:5780–5785. https://doi.org/10.1073/pnas.091415198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Global Burden of Disease Cancer C, Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, Hamadeh RR, Moore A, Werdecker A, Gessner BD, Te Ao B, McMahon B, Karimkhani C, Yu C, Cooke GS, Schwebel DC, Carpenter DO, Pereira DM, Nash D, Kazi DS, De Leo D, Plass D, Ukwaja KN, Thurston GD, Yun Jin K, Simard EP, Mills E, Park EK, Catala-Lopez F, deVeber G, Gotay C, Khan G, Hosgood HD 3rd, Santos IS, Leasher JL, Singh J, Leigh J, Jonas JB, Sanabria J, Beardsley J, Jacobsen KH, Takahashi K, Franklin RC, Ronfani L, Montico M, Naldi L, Tonelli M, Geleijnse J, Petzold M, Shrime MG, Younis M, Yonemoto N, Breitborde N, Yip P, Pourmalek F, Lotufo PA, Esteghamati A, Hankey GJ, Ali R, Lunevicius R, Malekzadeh R, Dellavalle R, Weintraub R, Lucas R, Hay R, Rojas-Rueda D, Westerman R, Sepanlou SG, Nolte S, Patten S, Weichenthal S, Abera SF, Fereshtehnejad SM, Shiue I, Driscoll T, Vasankari T, Alsharif U, Rahimi-Movaghar V, Vlassov VV, Marcenes WS, Mekonnen W, Melaku YA, Yano Y, Artaman A, Campos I, MacLachlan J, Mueller U, Kim D, Trillini M, Eshrati B, Williams HC, Shibuya K, Dandona R, Murthy K, Cowie B et al (2015) The global burden of cancer 2013. JAMA Oncol 1:505–527. https://doi.org/10.1001/jamaoncol.2015.0735

    Article  Google Scholar 

  32. Greer EL, Shi Y (2012) Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet 13:343–357. https://doi.org/10.1038/nrg3173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Guo L, Zheng X, Wang E, Jia X, Wang G, Wen J (2020) Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425. Biomed Pharmacother 125:109784. https://doi.org/10.1016/j.biopha.2019.109784

    Article  CAS  PubMed  Google Scholar 

  34. Gupta SK, Garg A, Avramopoulos P, Engelhardt S, Streckfuss-Bömeke K, Batkai S, Thum T (2019) miR-212/132 cluster modulation prevents doxorubicin-mediated atrophy and cardiotoxicity. Mol Ther 27:17–28. https://doi.org/10.1016/j.ymthe.2018.11.004

    Article  CAS  PubMed  Google Scholar 

  35. Gupta SK, Garg A, Bär C, Chatterjee S, Foinquinos A, Milting H, Streckfuß-Bömeke K, Fiedler J, Thum T (2018) Quaking inhibits doxorubicin-mediated cardiotoxicity through regulation of cardiac circular RNA expression. Circ Res 122:246–254. https://doi.org/10.1161/circresaha.117.311335

    Article  CAS  PubMed  Google Scholar 

  36. Han D, Wang Y, Wang Y, Dai X, Zhou T, Chen J, Tao B, Zhang J, Cao F (2020) The tumor-suppressive human circular RNA CircITCH sponges miR-330-5p to ameliorate doxorubicin-induced cardiotoxicity through upregulating SIRT6, survivin, and SERCA2a. Circ Res 127:e108–e125. https://doi.org/10.1161/CIRCRESAHA.119.316061

    Article  CAS  PubMed  Google Scholar 

  37. Hanf A, Oelze M, Manea A, Li H, Munzel T, Daiber A (2019) The anti-cancer drug doxorubicin induces substantial epigenetic changes in cultured cardiomyocytes. Chem Biol Interact 313:108834. https://doi.org/10.1016/j.cbi.2019.108834

    Article  CAS  PubMed  Google Scholar 

  38. Herr DJ, Singh T, Dhammu T, Menick DR (2020) Regulation of metabolism by mitochondrial enzyme acetylation in cardiac ischemia–reperfusion injury. Biochim Biophys Acta Mol Basis Dis 1866:165728. https://doi.org/10.1016/j.bbadis.2020.165728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Heusch G (2023) Cardioprotection in cardio-oncology: a case for concern? Cardiovasc Res 119:e144–e145. https://doi.org/10.1093/cvr/cvad111

    Article  CAS  PubMed  Google Scholar 

  40. Heusch G, Andreadou I, Bell R, Bertero E, Botker HE, Davidson SM, Downey J, Eaton P, Ferdinandy P, Gersh BJ, Giacca M, Hausenloy DJ, Ibanez B, Krieg T, Maack C, Schulz R, Sellke F, Shah AM, Thiele H, Yellon DM, Di Lisa F (2023) Health position paper and redox perspectives on reactive oxygen species as signals and targets of cardioprotection. Redox Biol 67:102894. https://doi.org/10.1016/j.redox.2023.102894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99:365–375. https://doi.org/10.1093/jnci/djk064

    Article  PubMed  Google Scholar 

  42. Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, Hasegawa K, Kita T, Kimura T (2010) Acute doxorubicin cardiotoxicity is associated with miR-146a-induced inhibition of the neuregulin-ErbB pathway. Cardiovasc Res 87:656–664. https://doi.org/10.1093/cvr/cvq148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ilango S, Paital B, Jayachandran P, Padma PR, Nirmaladevi R (2020) Epigenetic alterations in cancer. Front Biosci (Landmark Ed) 25:1058–1109. https://doi.org/10.2741/4847

    Article  CAS  PubMed  Google Scholar 

  44. Jahng JWS, Liu L, Wu JC (2020) Tumor repressor circular RNA as a new target for preventative gene therapy against doxorubicin-induced cardiotoxicity. Circ Res 127:483–485. https://doi.org/10.1161/CIRCRESAHA.120.317568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jambhekar A, Dhall A, Shi Y (2019) Roles and regulation of histone methylation in animal development. Nat Rev Mol Cell Biol 20:625–641. https://doi.org/10.1038/s41580-019-0151-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Jang J, Song G, Pettit SM, Li Q, Song X, Cai CL, Kaushal S, Li D (2022) Epicardial HDAC3 promotes myocardial growth through a novel microRNA pathway. Circ Res 131:151–164. https://doi.org/10.1161/CIRCRESAHA.122.320785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jones PA, Ohtani H, Chakravarthy A, De Carvalho DD (2019) Epigenetic therapy in immune-oncology. Nat Rev Cancer 19:151–161. https://doi.org/10.1038/s41568-019-0109-9

    Article  CAS  PubMed  Google Scholar 

  48. Kietzmann T, Petry A, Shvetsova A, Gerhold JM, Görlach A (2017) The epigenetic landscape related to reactive oxygen species formation in the cardiovascular system. Br J Pharmacol 174:1533–1554. https://doi.org/10.1111/bph.13792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kim SW, Ahn BY, Tran TTV, Pyun JH, Kang JS, Leem YE (2022) PRMT1 suppresses doxorubicin-induced cardiotoxicity by inhibiting endoplasmic reticulum stress. Cell Signal 98:110412. https://doi.org/10.1016/j.cellsig.2022.110412

    Article  CAS  PubMed  Google Scholar 

  50. Kitakata H, Endo J, Ikura H, Moriyama H, Shirakawa K, Katsumata Y, Sano M (2022) Therapeutic targets for DOX-induced cardiomyopathy: role of apoptosis vs. ferroptosis. Int J Mol Sci 23:1414. https://doi.org/10.3390/ijms23031414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Komal S, Zhang LR, Han SN (2021) Potential regulatory role of epigenetic RNA methylation in cardiovascular diseases. Biomed Pharmacother 137:111376. https://doi.org/10.1016/j.biopha.2021.111376

    Article  CAS  PubMed  Google Scholar 

  52. Kumari H, Huang WH, Chan MWY (2020) Review on the role of epigenetic modifications in doxorubicin-induced cardiotoxicity. Front Cardiovasc Med 7:56. https://doi.org/10.3389/fcvm.2020.00056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kuno A, Hosoda R, Tsukamoto M, Sato T, Sakuragi H, Ajima N, Saga Y, Tada K, Taniguchi Y, Iwahara N, Horio Y (2022) SIRT1 in the cardiomyocyte counteracts doxorubicin-induced cardiotoxicity via regulating histone H2AX. Cardiovasc Res 118:3360–3373. https://doi.org/10.1093/cvr/cvac026

    Article  CAS  Google Scholar 

  54. Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M (2014) Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. J Am Coll Cardiol 63:809–816. https://doi.org/10.1016/j.jacc.2013.10.061

    Article  CAS  PubMed  Google Scholar 

  55. Le P, Kunold E, Macsics R, Rox K, Jennings MC, Ugur I, Reinecke M, Chaves-Moreno D, Hackl MW, Fetzer C, Mandl FAM, Lehmann J, Korotkov VS, Hacker SM, Kuster B, Antes I, Pieper DH, Rohde M, Wuest WM, Medina E, Sieber SA (2020) Repurposing human kinase inhibitors to create an antibiotic active against drug-resistant Staphylococcus aureus, persisters and biofilms. Nat Chem 12:145–158. https://doi.org/10.1038/s41557-019-0378-7

    Article  CAS  PubMed  Google Scholar 

  56. Levis BE, Binkley PF, Shapiro CL (2017) Cardiotoxic effects of anthracycline-based therapy: what is the evidence and what are the potential harms? Lancet Oncol 18:e445–e456. https://doi.org/10.1016/s1470-2045(17)30535-1

    Article  CAS  PubMed  Google Scholar 

  57. Li D, Yang Y, Wang S, He X, Liu M, Bai B, Tian C, Sun R, Yu T, Chu X (2021) Role of acetylation in doxorubicin-induced cardiotoxicity. Redox Biol 46:102089. https://doi.org/10.1016/j.redox.2021.102089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Li H, Zhang M, Wang Y, Gong K, Yan T, Wang D, Meng X, Yang X, Chen Y, Han J, Duan Y, Zhang S (2022) Daidzein alleviates doxorubicin-induced heart failure via the SIRT3/FOXO3a signaling pathway. Food Funct 13:9576–9588. https://doi.org/10.1039/d2fo00772j

    Article  CAS  PubMed  Google Scholar 

  59. Li L, Yang XJ (2015) Tubulin acetylation: responsible enzymes, biological functions and human diseases. Cell Mol Life Sci 72:4237–4255. https://doi.org/10.1007/s00018-015-2000-5

    Article  CAS  PubMed  Google Scholar 

  60. Li P, Ge J, Li H (2020) Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease. Nat Rev Cardiol 17:96–115. https://doi.org/10.1038/s41569-019-0235-9

    Article  CAS  PubMed  Google Scholar 

  61. Li Q, Qin M, Tan Q, Li T, Gu Z, Huang P, Ren L (2020) MicroRNA-129-1-3p protects cardiomyocytes from pirarubicin-induced apoptosis by down-regulating the GRIN2D-mediated Ca(2+) signalling pathway. J Cell Mol Med 24:2260–2271. https://doi.org/10.1111/jcmm.14908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Li W, Fu Y, Wang W (2024) A real-world pharmacovigilance study investigating the toxicities of histone deacetylase inhibitors. Ann Hematol. https://doi.org/10.1007/s00277-024-05691-2

    Article  PubMed  PubMed Central  Google Scholar 

  63. Liu J, Wu X, Wang X, Zhang Y, Bu P, Zhang Q, Jiang F (2013) Global gene expression profiling reveals functional importance of Sirt2 in endothelial cells under oxidative stress. Int J Mol Sci 14:5633–5649. https://doi.org/10.3390/ijms14035633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lu D, Chatterjee S, Xiao K, Riedel I, Huang CK, Costa A, Cushman S, Neufeldt D, Rode L, Schmidt A, Juchem M, Leonardy J, Buchler G, Blume J, Gern OL, Kalinke U, Wen Tan WL, Foo R, Vink A, van Laake LW, van der Meer P, Bar C, Thum T (2022) A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. Eur Heart J 43:4496–4511. https://doi.org/10.1093/eurheartj/ehac337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ma J, Wang Y, Zheng D, Wei M, Xu H, Peng T (2013) Rac1 signalling mediates doxorubicin-induced cardiotoxicity through both reactive oxygen species-dependent and -independent pathways. Cardiovasc Res 97:77–87. https://doi.org/10.1093/cvr/cvs309

    Article  CAS  PubMed  Google Scholar 

  66. Ma Y, Liu X, Bi Y, Wang T, Chen C, Wang Y, Han D, Cao F (2022) Alteration of N(6)-methyladenosine mRNA methylation in a human stem cell-derived cardiomyocyte model of tyrosine kinase inhibitor-induced cardiotoxicity. Front Cardiovasc Med 9:849175. https://doi.org/10.3389/fcvm.2022.849175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Meng J, Xu C (2022) MicroRNA-495-3p diminishes doxorubicin-induced cardiotoxicity through activating AKT. J Cell Mol Med 26:2076–2088. https://doi.org/10.1111/jcmm.17230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Morel D, Jeffery D, Aspeslagh S, Almouzni G, Postel-Vinay S (2019) Combining epigenetic drugs with other therapies for solid tumours—past lessons and future promise. Nat Rev Clin Oncol 17:91–107. https://doi.org/10.1038/s41571-019-0267-4

    Article  CAS  PubMed  Google Scholar 

  69. Morel D, Jeffery D, Aspeslagh S, Almouzni G, Postel-Vinay S (2020) Combining epigenetic drugs with other therapies for solid tumours—past lessons and future promise. Nat Rev Clin Oncol 17:91–107. https://doi.org/10.1038/s41571-019-0267-4

    Article  CAS  PubMed  Google Scholar 

  70. Mosele F, Stefanovska B, Lusque A, Tran Dien A, Garberis I, Droin N, Le Tourneau C, Sablin MP, Lacroix L, Enrico D, Miran I, Jovelet C, Bièche I, Soria JC, Bertucci F, Bonnefoi H, Campone M, Dalenc F, Bachelot T, Jacquet A, Jimenez M, André F (2020) Outcome and molecular landscape of patients with PIK3CA-mutated metastatic breast cancer. Ann Oncol 31:377–386. https://doi.org/10.1016/j.annonc.2019.11.006

    Article  CAS  PubMed  Google Scholar 

  71. Nguyen N, Lienhard M, Herwig R, Kleinjans J, Jennen D (2022) Epirubicin alters DNA methylation profiles related to cardiotoxicity. Front Biosci (Landmark Ed) 27:173. https://doi.org/10.31083/j.fbl2706173

    Article  CAS  PubMed  Google Scholar 

  72. Nguyen N, Souza T, Kleinjans J, Jennen D (2022) Transcriptome analysis of long noncoding RNAs reveals their potential roles in anthracycline-induced cardiotoxicity. Noncoding RNA Res 7:106–113. https://doi.org/10.1016/j.ncrna.2022.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ordovás JM, Smith CE (2010) Epigenetics and cardiovascular disease. Nat Rev Cardiol 7:510–519. https://doi.org/10.1038/nrcardio.2010.104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Pakravan G, Foroughmand AM, Peymani M, Ghaedi K, Hashemi M-S, Hajjari M, Nasr-Esfahani MH (2018) Downregulation of miR-130a, antagonized doxorubicin-induced cardiotoxicity via increasing the PPARγ expression in mESCs-derived cardiac cells. Cell Death Dis 9:758. https://doi.org/10.1038/s41419-018-0797-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Pan JA, Tang Y, Yu JY, Zhang H, Zhang JF, Wang CQ, Gu J (2019) miR-146a attenuates apoptosis and modulates autophagy by targeting TAF9b/P53 pathway in doxorubicin-induced cardiotoxicity. Cell Death Dis 10:668. https://doi.org/10.1038/s41419-019-1901-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pan Y, Pan YM, Liu FT, Xu SL, Gu JT, Hang PZ, Du ZM (2021) MicroRNA-98 ameliorates doxorubicin-induced cardiotoxicity via regulating caspase-8 dependent Fas/RIP3 pathway. Environ Toxicol Pharmacol 85:103624. https://doi.org/10.1016/j.etap.2021.103624

    Article  CAS  PubMed  Google Scholar 

  77. Papazoglou P, Peng L, Sachinidis A (2021) Epigenetic mechanisms involved in the cardiovascular toxicity of anticancer drugs. Front Cardiovasc Med 8:658900. https://doi.org/10.3389/fcvm.2021.658900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Peng L, Qian M, Liu Z, Tang X, Sun J, Jiang Y, Sun S, Cao X, Pang Q, Liu B (2020) Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis. Nucleic Acids Res 48:4992–5005. https://doi.org/10.1093/nar/gkaa214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pillai VB, Bindu S, Sharp W, Fang YH, Kim G, Gupta M, Samant S, Gupta MP (2016) Sirt3 protects mitochondrial DNA damage and blocks the development of doxorubicin-induced cardiomyopathy in mice. Am J Physiol Heart Circ Physiol 310:H962-972. https://doi.org/10.1152/ajpheart.00832.2015

    Article  PubMed  PubMed Central  Google Scholar 

  80. Robinson EL, Ameri P, Delrue L, Vanderheyden M, Bartunek J, Altieri P, Heymans S, Heggermont WA (2023) Differential expression of epigenetic modifiers in early and late cardiotoxic heart failure reveals DNA methylation as a key regulator of cardiotoxicity. Front Cardiovasc Med 10:884174. https://doi.org/10.3389/fcvm.2023.884174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Roca-Alonso L, Castellano L, Mills A, Dabrowska AF, Sikkel MB, Pellegrino L, Jacob J, Frampton AE, Krell J, Coombes RC, Harding SE, Lyon AR, Stebbing J (2015) Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis. Cell Death Dis 6:e1754–e1754. https://doi.org/10.1038/cddis.2015.89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Roundtree IA, Evans ME, Pan T, He C (2017) Dynamic RNA modifications in gene expression regulation. Cell 169:1187–1200. https://doi.org/10.1016/j.cell.2017.05.045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Roychoudhury S, Kumar A, Bhatkar D, Sharma NK (2020) Molecular avenues in targeted doxorubicin cancer therapy. Future Oncol 16:687–700. https://doi.org/10.2217/fon-2019-0458

    Article  CAS  PubMed  Google Scholar 

  84. Sabari BR, Zhang D, Allis CD, Zhao Y (2017) Metabolic regulation of gene expression through histone acylations. Nat Rev Mol Cell Biol 18:90–101. https://doi.org/10.1038/nrm.2016.140

    Article  CAS  PubMed  Google Scholar 

  85. Salem JE, Nguyen LS, Moslehi JJ, Ederhy S, Lebrun-Vignes B, Roden DM, Funck-Brentano C, Gougis P (2021) Anticancer drug-induced life-threatening ventricular arrhythmias: a World Health Organization pharmacovigilance study. Eur Heart J 42:3915–3928. https://doi.org/10.1093/eurheartj/ehab362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sawicki KT, Sala V, Prever L, Hirsch E, Ardehali H, Ghigo A (2021) Preventing and treating anthracycline cardiotoxicity: new insights. Annu Rev Pharmacol Toxicol 61:309–332. https://doi.org/10.1146/annurev-pharmtox-030620-104842

    Article  CAS  PubMed  Google Scholar 

  87. Scott JM, Khakoo A, Mackey JR, Haykowsky MJ, Douglas PS, Jones LW (2011) Modulation of anthracycline-induced cardiotoxicity by aerobic exercise in breast cancer: current evidence and underlying mechanisms. Circulation 124:642–650. https://doi.org/10.1161/circulationaha.111.021774

    Article  PubMed  PubMed Central  Google Scholar 

  88. Shen X, Zhi F, Shi C, Xu J, Chao Y, Xu J, Jiang Y, Bai Y, Yang B (2023) The involvement and therapeutic potential of lncRNA Kcnq1ot1/miR-34a-5p/Sirt1 pathway in arsenic trioxide-induced cardiotoxicity. J Transl Med 21:52. https://doi.org/10.1186/s12967-023-03895-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Shi Y, Zhang H, Huang S, Yin L, Wang F, Luo P, Huang H (2022) Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials. Signal Transduct Target Ther 7:200. https://doi.org/10.1038/s41392-022-01055-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Shvedunova M, Akhtar A (2022) Modulation of cellular processes by histone and non-histone protein acetylation. Nat Rev Mol Cell Biol 23:329–349. https://doi.org/10.1038/s41580-021-00441-y

    Article  CAS  PubMed  Google Scholar 

  91. Sin TK, Tam BT, Yung BY, Yip SP, Chan LW, Wong CS, Ying M, Rudd JA, Siu PM (2015) Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1-USP7 axis. J Physiol 593:1887–1899. https://doi.org/10.1113/jphysiol.2014.270101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Sinniah E, Wu Z, Shen S, Naval-Sanchez M, Chen X, Lim J, Helfer A, Iyer A, Tng J, Lucke AJ, Reid RC, Redd MA, Nefzger CM, Fairlie DP, Palpant NJ (2022) Temporal perturbation of histone deacetylase activity reveals a requirement for HDAC1-3 in mesendoderm cell differentiation. Cell Rep 39:110818. https://doi.org/10.1016/j.celrep.2022.110818

    Article  CAS  PubMed  Google Scholar 

  93. Song R, Yang Y, Lei H, Wang G, Huang Y, Xue W, Wang Y, Yao L, Zhu Y (2018) HDAC6 inhibition protects cardiomyocytes against doxorubicin-induced acute damage by improving alpha-tubulin acetylation. J Mol Cell Cardiol 124:58–69. https://doi.org/10.1016/j.yjmcc.2018.10.007

    Article  CAS  PubMed  Google Scholar 

  94. Stamm P, Kirmes I, Palmer A, Molitor M, Kvandova M, Kalinovic S, Mihalikova D, Reid G, Wenzel P, Münzel T, Daiber A, Jansen T (2021) Doxorubicin induces wide-spread transcriptional changes in the myocardium of hearts distinguishing between mice with preserved and impaired cardiac function. Life Sci 284:119879. https://doi.org/10.1016/j.lfs.2021.119879

    Article  CAS  PubMed  Google Scholar 

  95. Sun Z, Lu W, Lin N, Lin H, Zhang J, Ni T, Meng L, Zhang C, Guo H (2020) Dihydromyricetin alleviates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome through activation of SIRT1. Biochem Pharmacol 175:113888. https://doi.org/10.1016/j.bcp.2020.113888

    Article  CAS  PubMed  Google Scholar 

  96. Tian L, Wu D, Dasgupta A, Chen KH, Mewburn J, Potus F, Lima PDA, Hong Z, Zhao YY, Hindmarch CCT, Kutty S, Provencher S, Bonnet S, Sutendra G, Archer SL (2020) Epigenetic metabolic reprogramming of right ventricular fibroblasts in pulmonary arterial hypertension: a pyruvate dehydrogenase kinase-dependent shift in mitochondrial metabolism promotes right ventricular fibrosis. Circ Res 126:1723–1745. https://doi.org/10.1161/CIRCRESAHA.120.316443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Tian S, Lei I, Gao W, Liu L, Guo Y, Creech J, Herron TJ, Xian S, Ma PX, Eugene Chen Y, Li Y, Alam HB, Wang Z (2019) HDAC inhibitor valproic acid protects heart function through Foxm1 pathway after acute myocardial infarction. EBioMedicine 39:83–94. https://doi.org/10.1016/j.ebiom.2018.12.003

    Article  PubMed  Google Scholar 

  98. Totzeck M, Schuler M, Stuschke M, Heusch G, Rassaf T (2019) Cardio-oncology—strategies for management of cancer-therapy related cardiovascular disease. Int J Cardiol 280:163–175. https://doi.org/10.1016/j.ijcard.2019.01.038

    Article  PubMed  Google Scholar 

  99. Tseng AH, Shieh SS, Wang DL (2013) SIRT3 deacetylates FOXO3 to protect mitochondria against oxidative damage. Free Radic Biol Med 63:222–234. https://doi.org/10.1016/j.freeradbiomed.2013.05.002

    Article  CAS  PubMed  Google Scholar 

  100. Vejpongsa P, Yeh ET (2014) Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol 64:938–945. https://doi.org/10.1016/j.jacc.2014.06.1167

    Article  CAS  PubMed  Google Scholar 

  101. Wallace KB, Sardão VA, Oliveira PJ (2020) Mitochondrial determinants of doxorubicin-induced cardiomyopathy. Circ Res 126:926–941. https://doi.org/10.1161/circresaha.119.314681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wan Q, Xu T, Ding W, Zhang X, Ji X, Yu T, Yu W, Lin Z, Wang J (2019) miR-499-5p attenuates mitochondrial fission and cell apoptosis via p21 in doxorubicin cardiotoxicity. Front Genet 9:734. https://doi.org/10.3389/fgene.2018.00734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Wang JX, Zhang XJ, Feng C, Sun T, Wang K, Wang Y, Zhou LY, Li PF (2015) MicroRNA-532-3p regulates mitochondrial fission through targeting apoptosis repressor with caspase recruitment domain in doxorubicin cardiotoxicity. Cell Death Dis 6:e1677–e1677. https://doi.org/10.1038/cddis.2015.41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Wang L, Yu P, Wang J, Xu G, Wang T, Feng J, Bei Y, Xu J, Wang H, Das S, Xiao J (2022) Downregulation of circ-ZNF609 promotes heart repair by modulating RNA N(6)-methyladenosine-modified yap expression. Research (Washington, DC) 2022:9825916. https://doi.org/10.34133/2022/9825916

    Article  CAS  Google Scholar 

  105. Wang P, Lan R, Guo Z, Cai S, Wang J, Wang Q, Li Z, Li Z, Wang Q, Li J, Wu Z, Lu J, Liu P (2020) Histone demethylase JMJD3 mediated doxorubicin-induced cardiomyopathy by suppressing SESN2 expression. Front Cell Dev Biol 8:548605. https://doi.org/10.3389/fcell.2020.548605

    Article  PubMed  PubMed Central  Google Scholar 

  106. Wang S, Wang Y, Zhang Z, Liu Q, Gu J (2017) Cardioprotective effects of fibroblast growth factor 21 against doxorubicin-induced toxicity via the SIRT1/LKB1/AMPK pathway. Cell Death Dis 8:e3018. https://doi.org/10.1038/cddis.2017.410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wang X, Cheng Z, Xu J, Feng M, Zhang H, Zhang L, Qian L (2021) Circular RNA Arhgap12 modulates doxorubicin-induced cardiotoxicity by sponging miR-135a-5p. Life Sci 265:118788. https://doi.org/10.1016/j.lfs.2020.118788

    Article  CAS  PubMed  Google Scholar 

  108. Wang XX, Wang XL, Tong MM, Gan L, Chen H, Wu SS, Chen JX, Li RL, Wu Y, Zhang HY, Zhu Y, Li YX, He JH, Wang M, Jiang W (2016) SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Res Cardiol 111:13. https://doi.org/10.1007/s00395-016-0531-z

    Article  CAS  PubMed  Google Scholar 

  109. Wang YY, Gao B, Yang Y, Jia SB, Ma XP, Zhang MH, Wang LJ, Ma AQ, Zhang QN (2022) Histone deacetylase 3 suppresses the expression of SHP-1 via deacetylation of DNMT1 to promote heart failure. Life Sci 292:119552. https://doi.org/10.1016/j.lfs.2021.119552

    Article  CAS  PubMed  Google Scholar 

  110. Wei J, He C (2021) Chromatin and transcriptional regulation by reversible RNA methylation. Curr Opin Cell Biol 70:109–115. https://doi.org/10.1016/j.ceb.2020.11.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Wojnowski L, Kulle B, Schirmer M, Schlüter G, Schmidt A, Rosenberger A, Vonhof S, Bickeböller H, Toliat MR, Suk EK, Tzvetkov M, Kruger A, Seifert S, Kloess M, Hahn H, Loeffler M, Nürnberg P, Pfreundschuh M, Trümper L, Brockmöller J, Hasenfuss G (2005) NAD(P)H oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation 112:3754–3762. https://doi.org/10.1161/circulationaha.105.576850

    Article  CAS  PubMed  Google Scholar 

  112. Wu S, Wang X, Tong M, Fu L, Zhang Y, Xu J, Chen X, Chen H, Li R, Wu Y, Xin J, Yan X, Li H, Lan J, Xue K, Li X, Zhuo C, Wei J (2021) Sirt6 protects cardiomyocytes against doxorubicininduced cardiotoxicity by inhibiting P53/Fasdependent cell death and augmenting endogenous antioxidant defense mechanisms. Cell Biol Toxicol 39:237–258. https://doi.org/10.21203/rs.3.rs-263382/v1

    Article  PubMed  Google Scholar 

  113. Wu TT, Ma YW, Zhang X, Dong W, Gao S, Wang JZ, Zhang LF, Lu D (2020) Myocardial tissue-specific Dnmt1 knockout in rats protects against pathological injury induced by Adriamycin. Lab Invest 100:974–985. https://doi.org/10.1038/s41374-020-0402-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Xie Z, Xia W, Hou M (2018) Long intergenic noncoding RNAp21 mediates cardiac senescence via the Wnt/betacatenin signaling pathway in doxorubicin-induced cardiotoxicity. Mol Med Rep 17:2695–2704. https://doi.org/10.3892/mmr.2017.8169

    Article  CAS  PubMed  Google Scholar 

  115. Yan H, Bu P (2021) Non-coding RNA in cancer. Essays Biochem 65:625–639. https://doi.org/10.1042/ebc20200032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yang L, Yu Y, Tian G, Deng H, Yu B (2021) H3K9ac modification was involved in doxorubicin induced apoptosis by regulating Pik3ca transcription in H9C2 cells. Life Sci 284:119107. https://doi.org/10.1016/j.lfs.2021.119107

    Article  CAS  PubMed  Google Scholar 

  117. Yang Y, Li N, Chen T, Zhang C, Li J, Liu L, Qi Y, Zheng X, Zhang C, Bu P (2019) Sirt3 promotes sensitivity to sunitinib-induced cardiotoxicity via inhibition of GTSP1/JNK/autophagy pathway in vivo and in vitro. Arch Toxicol 93:3249–3260. https://doi.org/10.1007/s00204-019-02573-9

    Article  CAS  PubMed  Google Scholar 

  118. Yin Z, Zhao Y, Li H, Yan M, Zhou L, Chen C, Wang DW (2016) miR-320a mediates doxorubicin-induced cardiotoxicity by targeting VEGF signal pathway. Aging (Albany NY) 8:192–207. https://doi.org/10.18632/aging.100876

    Article  CAS  PubMed  Google Scholar 

  119. Yu P, Wang J, Xu GE, Zhao X, Cui X, Feng J, Sun J, Wang T, Spanos M, Lehmann HI, Li G, Xu J, Wang L, Xiao J (2023) RNA m(6)A-regulated circ-ZNF609 suppression ameliorates doxorubicin-induced cardiotoxicity by upregulating FTO. JACC Basic Transl Sci 8:677–698. https://doi.org/10.1016/j.jacbts.2022.12.005

    Article  PubMed  PubMed Central  Google Scholar 

  120. Zhang C, Feng Y, Qu S, Wei X, Zhu H, Luo Q, Liu M, Chen G, Xiao X (2011) Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53. Cardiovasc Res 90:538–545. https://doi.org/10.1093/cvr/cvr022

    Article  CAS  PubMed  Google Scholar 

  121. Zhang L, Liu L, Li X (2020) MiR-526b-3p mediates doxorubicin-induced cardiotoxicity by targeting STAT3 to inactivate VEGFA. Biomed Pharmacother 123:109751. https://doi.org/10.1016/j.biopha.2019.109751

    Article  CAS  PubMed  Google Scholar 

  122. Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET (2012) Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med 18:1639–1642. https://doi.org/10.1038/nm.2919

    Article  CAS  PubMed  Google Scholar 

  123. Zhang WB, Lai X, Guo XF (2021) Activation of Nrf2 by miR-152 inhibits doxorubicin-induced cardiotoxicity via attenuation of oxidative stress, inflammation, and apoptosis. Oxid Med Cell Longev 2021:8860883. https://doi.org/10.1155/2021/8860883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Zhao L, Tao X, Qi Y, Xu L, Yin L, Peng J (2018) Protective effect of dioscin against doxorubicin-induced cardiotoxicity via adjusting microRNA-140-5p-mediated myocardial oxidative stress. Redox Biol 16:189–198. https://doi.org/10.1016/j.redox.2018.02.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Zhao Z, He J, Zhang J, Liu M, Yang S, Li N, Li X (2014) Dysregulated miR1254 and miR579 for cardiotoxicity in patients treated with bevacizumab in colorectal cancer. Tumour Biol 35:5227–5235. https://doi.org/10.1007/s13277-014-1679-5

    Article  CAS  PubMed  Google Scholar 

  126. Zhou M, Sun X, Wang C, Wang F, Fang C, Hu Z (2022) PFKM inhibits doxorubicin-induced cardiotoxicity by enhancing oxidative phosphorylation and glycolysis. Sci Rep 12:11684. https://doi.org/10.1038/s41598-022-15743-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhu J-N, Fu Y-H, Hu Z-q, Li W-Y, Tang C-M, Fei H-W, Yang H, Lin Q-x, Gou D-M, Wu S-L, Shan Z-X (2017) Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity. Sci Rep 7:11879. https://doi.org/10.1038/s41598-017-12192-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Zhu M, Liu Y, Song Y, Zhang S, Hang C, Wu F, Lin X, Huang Z, Lan F, Xu M (2021) The role of METTL3-mediated N6-methyladenosine (m6A) of JPH2 mRNA in cyclophosphamide-induced cardiotoxicity. Front Cardiovasc Med 8:763469. https://doi.org/10.3389/fcvm.2021.763469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Huang-Tian Yang (Shanghai Institute of Nutrition and Health) for constructive comments on this manuscript. This work was supported by the National Natural Science Foundation of China Grants (Grant numbers U21A20336, 81820108031, and 91939301); the National Key Research and Development Program of China (Grant number 2022YFC3602400); the Beijing Municipal Natural Science Foundation Grants (Grant number 7222218); and the medical research management/basic and clinical research unit of metabolic cardiovascular diseases, Chinese Academy of Medical Sciences Grant (Grant number 2021RU003).

Author information

Authors and Affiliations

  1. Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China

    Xuening Liu & Zijian Li

  2. Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China

    Xuening Liu & Zijian Li

  3. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, China

    Zijian Li

Authors
  1. Xuening Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zijian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xuening Liu performed the literature search and wrote the manuscript. Zijian Li reviewed and edited the manuscript before submission.

Corresponding author

Correspondence to Zijian Li.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

The manuscript does not contain clinical studies or patient data.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Li, Z. The role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity. Basic Res Cardiol (2024). https://doi.org/10.1007/s00395-024-01054-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00395-024-01054-0

Keywords

Search

Navigation