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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

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