Role of the long intergenic non-coding (linc) RNA NRON in cardiac disease
Final Report Abstract
Main objective of this research project is to understand the role of long non coding RNA NRON in cardiomyocyte biology and NFAT. During the course of study we made an interesting observation that NFAT regulates a novel lncRNA CHAST, which is upregulated during cardiac hypertrophy. We performed in depth studies to understand the mechanism of both NRON and CHAST regulation and their role in murine and human cardiac hypertrophy. Our studies indicated that both NRON and CHAST is a promising therapeutic target for inhibition of cardiac hypertrophy and failure. The studies have very high translational significance. Intellectual property rights for the above finding have been protected by patent filings. Prof. Thomas Thum is performing further studies for validation and clinical development of CHAST and NRON based therapeutics/ diagnostics for heart failure.
Publications
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Non-coding RNAs in cardiac remodeling and heart failure. Circulation Research. 2013 Aug 30;113(6):676-89
Kumarswamy R, Thum T
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Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circulation Research. 2014 May 9;114(10):1569-75
Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, Lemesle G, de Groote P, Pinet F, Thum T
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Long noncoding RNAs as inducers and terminators of vascular development. Circulation. 2015 Apr 7;131(14):1236-8
Viereck J, Kumarswamy R, Thum T
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Long noncoding RNA Chast promotes cardiac remodeling. Science Translational Medicine. 2016 Feb 17;8(326):326ra22
Viereck J, Kumarswamy R, Foinquinos A, Xiao K, Avramopoulos P, Kunz M, Dittrich M, Maetzig T, Zimmer K, Remke J, Just A, Fendrich J, Scherf K, Bolesani E, Schambach A, Weidemann F, Zweigerdt R, de Windt LJ, Engelhardt S, Dandekar T, Batkai S, Thum T