Abstract
Circular RNA (circRNA) is a novel class of noncoding RNAs, and the roles of circRNAs in the development of cardiac hypertrophy remain to be explored. Here, we investigate the potential roles of circRNAs in cardiac hypertrophy. By circRNA sequencing in left ventricular specimens collected from 8-week-old mice with isoproterenol hydrochloride-induced cardiac hypertrophy, we found 401 out of 3323 total circRNAs were dysregulated in the hypertrophic hearts compared with the controls. Of these, 303 circRNAs were upregulated and 98 were downregulated. Moreover, the GO and KEGG analyses revealed that the majority of parental gene of differentially expressed circRNAs were not only related to biological process such as metabolic process and response to stimulus, but also related to pathway such as circulatory system and cardiovascular diseases. On the other hand, total 1974 miRNAs were predicted to binding to these differentially expressed circRNAs, and the possible target mRNAs of those miRNAs were also predicted and analyzed in terms of functional annotation. Finally, we identified that ANF and miR-23a are downstream targets of circRNA wwp1, suggesting that circRNA wwp1 exerts inhibitory roles of cardiac hypertrophy via down-regulation of ANF and miR-23a, which underlying the potential mechanisms whereby circRNA regulates cardiac hypertrophy.
Highlights
Cardiac hypertrophy is an adaptive response to various physiological and pathologic stimuli; chronic, prolonged stress will lead to irreversible pathological hypertrophy, accompanied by myocardial dysfunction, and eventually heart failure [1]
We show for the first time that isoproterenol induces profound alterations in circRNA expression in the heart and, most importantly, that the majority of these circRNAs are novel and have not been previously reported before
This analysis of the cardiac hypertrophy response induced by isoproterenol suggests that the function of these circRNAs is linked to cardiac hypertrophy
Summary
Cardiac hypertrophy is an adaptive response to various physiological and pathologic stimuli; chronic, prolonged stress will lead to irreversible pathological hypertrophy, accompanied by myocardial dysfunction, and eventually heart failure [1]. Intracellular signaling pathways regulating cardiac hypertrophy have been explored, including ERK1/2, AMPK, and protein kinase C [3]. Phosphatidylinositol-3 kinase (PI3K)-Akt is the main pathway because it account for an increase in protein synthesis during www.aging-us.com cardiac hypertrophy [4]. Metabolic alterations are investigated because there is an energy substrate shift from fatty acid to glucose accompanied pathological cardiac hypertrophy [4]. Many attempts have been made on signaling pathways and metabolic alterations, but the function of noncoding RNAs in cardiac hypertrophy deserves more attention
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
