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doi:10.22028/D291-37715
Titel: | MicroRNA-4732-3p Is Dysregulated in Breast Cancer Patients with Cardiotoxicity, and Its Therapeutic Delivery Protects the Heart from Doxorubicin-Induced Oxidative Stress in Rats |
VerfasserIn: | Sánchez-Sánchez, Rafael Reinal, Ignacio Peiró-Molina, Esteban Buigues, Marc Tejedor, Sandra Hernándiz, Amparo Selva, Marta Hervás, David Cañada, Antonio J. Dorronsoro, Akaitz Santaballa, Ana Salvador, Carmen Caiment, Florian Kleinjans, Jos Martínez-Dolz, Luis Moscoso, Isabel Lage, Ricardo González-Juanatey, José R. Panadero, Joaquín Aparicio-Puerta, Ernesto Bernad, Antonio Sepúlveda, Pilar |
Sprache: | Englisch |
Titel: | Antioxidants |
Bandnummer: | 11 |
Heft: | 10 |
Verlag/Plattform: | MDPI |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | cardiotoxicity doxorubicin miR-4732-3p oxidative stress fibrosis angiogenesis cardiac function TGFβ pathway Hippo signaling pathway |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | 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. |
DOI der Erstveröffentlichung: | 10.3390/antiox11101955 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-377156 hdl:20.500.11880/34143 http://dx.doi.org/10.22028/D291-37715 |
ISSN: | 2076-3921 |
Datum des Eintrags: | 27-Okt-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary Materials |
In Beziehung stehendes Objekt: | http://www.mdpi.com/article/10.3390/antiox11101955/s1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Medizinische Biometrie, Epidemiologie und medizinische Informatik |
Professur: | M - Keiner Professur zugeordnet |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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antioxidants-11-01955.pdf | 28,66 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons