心脏毒性
阿霉素
蒽环类
医学
乳腺癌
小RNA
心力衰竭
药理学
癌症
内科学
癌症研究
化疗
生物
生物化学
基因
作者
Rafael Sánchez-Sánchez,Ignacio Reinal,Esteban Peiró-Molina,Marc Buigues,Sandra Tejedor,Amparo Hernándiz,Marta Selva,David Hervás,Antonio Cañada,Akaitz Dorronsoro,Ana Santaballa,C. Salvador Coloma,Florian Caiment,Jos Kleinjans,Luis Martínez Dolz,Isabel Moscoso,Ricardo Lage,José Ramón González-Juanatey,Joaquín Panadero,Ernesto Aparicio‐Puerta,António Bernad,Pilar Sepúlveda
出处
期刊:Antioxidants
[MDPI AG]
日期:2022-09-30
卷期号:11 (10): 1955-1955
被引量:6
标识
DOI:10.3390/antiox11101955
摘要
Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFβ and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.
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