Abstract 20171: Long Non-Coding RNA Myocardial Infarction-Associated Transcript Promotes Cardiac Progenitor Cell Survival
Background: Long non-coding RNAs (lncRNAs) refer to an emerging class of RNAs that are more than 200 nucleotides long, with no or limited protein-coding capacity. An increasing number of studies have uncovered pivotal roles of lncRNAs in biological processes. Myocardial infarction-associated transcript (MIAT), also called Gomafu or RNCR2, is a conserved mammalian lncRNA. GWAS studies have revealed single nucleotide polymorphisms (SNP) in 6 loci of this gene that are strongly associated with the incidence of human myocardial infarction (MI). However, whether and how MIAT impacts on the pathogenesis of MI is unknown.
Methods & Results: MIAT is expressed in neonatal mouse heart and to a lesser extent in adult heart according to quantitative RT-PCR analyses. In a mouse MI model, MIAT starts to increase in 2 hours, peaks around 6 to 12 hours, and decreases to baseline at 24 hours post-MI. Fluorescent in situ hybridization (FISH) also revealed an increasing number of MIAT-expressing cells after MI. Moreover, RT-PCR analyses revealed preferential expression of MIAT in cardiosphere-derived cardiac progenitor cells (CPCs) compared to other isolated cardiac cells at baseline. Upregulation of MIAT was observed in CPCs challenged with H2O2, and overexpression of MIAT protected CPC from H2O2-induced cell death. In contrast, knockdown (KD) of MIAT significantly impaired cell survival in oxidative conditions in vitro (upon H2O2 treatment) and in vivo (in the ischemic/reperfused heart). Notably, bioinformatics prediction and RNA immunoprecipitation identified FUS (fused in sarcoma) as a novel MIAT-interacting protein. CPCs displays reduced cell viability and increased apoptosis under oxidative stress when FUS was knocked down and MIAT overexpression was not able to enhance cell survival in the absence of FUS, suggesting that the protective role of MIAT is mediated by FUS.
Conclusions: MIAT interacts with FUS and promotes CPC survival under oxidative stress.
Author Disclosures: L. Yang: None. Y. Yu: None. B.T. Arnone: None. C. Boriboun: None. J. Shi: None. G. Qin: None.
- © 2016 by American Heart Association, Inc.