Noncoding RNA based strategies to treat doxorubicin induced cardiotoxicity
Final Report Abstract
Cancer survivors very often face cardiovascular problems due to cardiotoxic effects of cancer treatments. Chemotherapy drug doxorubicin has been shown to exert dose-dependent cardiotoxicity and induce heart-failure. Aim of my proposal was to identify new therapeutic targets to treat doxorubicin-induced cardiotoxicity. I identified two new targets, a RNA-binding protein and a microRNA cluster which can prevent doxorubicin-induced cardiotoxicity. In independent studies using mouse model of doxorubicin-induced cardiotoxicity, I show that AAV9 mediated cardiac overexpression of RNA-binding protein or microRNA cluster can prevent detrimental effects of doxorubicin and improve cardiac function. Thus, I identified two new potential candidates capable of preventing doxorubicin-induced cardiotoxicity in a pre-clinical mouse model.
Publications
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Non-coding RNAs as orchestrators of autophagic processes. J Mol Cell Cardiol. 2016 Jun; 95:26-30
Gupta SK, Thum T
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Pre-Clinical Development of a MicroRNA- Based Therapy for Elderly Patients with Myocardial Infarction. J Am Coll Cardiol. 2016 Oct; 68(14):1557-1571
Gupta SK, Foinquinos A, Thum S, Remke J, Zimmer K, Bauters C, de Groote P, Boon RA, de windt LJ, Preissle S, Hein L, Batkai S, Pinet F, Thum T
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Inhibition of the Cardiac Fibroblast-Enriched lncRNA Meg3 Prevents Cardiac Fibrosis and Diastolic Dysfunction. Circ Res. 2017 Aug 18; 121(5):575-583
Piccoli MT, Gupta SK, Viereck J, Foinquinos A, Samolovac S, Kramer FL, Garg A, Remke J, Zimmer K, Batkai S, Thum T
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Quaking inhibits doxorubicin-mediated cardiotoxicity through regulation of cardiac circular RNA expression. Circ Res. 2018 Jan 19;122(2):246-254
Gupta SK, Garg A, Bär C, Chatterjee S, Foinquinos A, Milting H, Streckfuß-Bömeke K, Fiedler J, Thum T
