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Stress response factors as hub‐regulators of microRNA biogenesis: implication to the diseased heart
Authors:Veronika Gurianova  Dmytro Stroy  Rachele Ciccocioppo  Iveta Gasparova  Daniel Petrovic  Miroslav Soucek  Victor Dosenko  Peter Kruzliak
Institution:1. Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kiev, Ukraine;2. Clinica Medica I;3. Fondazione IRCCS Policlinico San Matteo, Università degli Studi di Pavia, Italy;4. Institute of Biology, Genetics and Medical Genetics, Faculty of Medicine, Comenius University and University Hospital, Bratislava, Slovak Republic;5. Institute of Histology and Embryology, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia;6. Second Department of Internal Medicine, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic;7. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovak Republic;8. Laboratory of Structural Biology and Proteomics, Faculty of Pharmacy, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic
Abstract:MicroRNAs (miRNAs) are important regulators of heart function and then an intriguing therapeutic target for plenty of diseases. The problem raised is that many data in this area are contradictory, thus limiting the use of miRNA‐based therapy. The goal of this review is to describe the hub‐mechanisms regulating the biogenesis and function of miRNAs, which could help in clarifying some contradictions in the miRNA world. With this scope, we analyse an array of factors, including several known agents of stress response, mediators of epigenetic changes, regulators of alternative splicing, RNA editing, protein synthesis and folding and proteolytic systems. All these factors are important in cardiovascular function and most of them regulate miRNA biogenesis, but their influence on miRNAs was shown for non‐cardiac cells or some specific cardiac pathologies. Finally, we consider that studying the stress response factors, which are upstream regulators of miRNA biogenesis, in the diseased heart could help in (1) explaining some contradictions concerning miRNAs in heart pathology, (2) making the role of miRNAs in pathogenesis of cardiovascular disease more clear, and therefore, (3) getting powerful targets for its molecular therapy. Copyright © 2015 John Wiley & Sons, Ltd.
Keywords:miRNAs biogenesis  stress response  hub‐mechanisms  cardiac pathophysiology
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