Please use this identifier to cite or link to this item: https://doi.org/10.1093/cvr/cvz130
Title: Targeting the highly abundant circular RNA circSlc8a1 in cardiomyocytes attenuates pressure overload induced hypertrophy.
Authors: LIM TINGSEN BENSON 
EDITA ALIWARGA 
LUU DANH ANH TUAN 
LI YIQING 
Ng, Shi Ling
Annadoray, Lavenniah
Sian, Stephanie
MATTHEW ANDREW ACKERS-JOHNSON 
ROGER FOO SIK YIN 
Issue Date: 22-May-2019
Publisher: Oxford University Press (OUP)
Citation: LIM TINGSEN BENSON, EDITA ALIWARGA, LUU DANH ANH TUAN, LI YIQING, Ng, Shi Ling, Annadoray, Lavenniah, Sian, Stephanie, MATTHEW ANDREW ACKERS-JOHNSON, ROGER FOO SIK YIN (2019-05-22). Targeting the highly abundant circular RNA circSlc8a1 in cardiomyocytes attenuates pressure overload induced hypertrophy.. Cardiovasc Res. ScholarBank@NUS Repository. https://doi.org/10.1093/cvr/cvz130
Abstract: AIMS: We and others have previously described the expression landscape of circular RNA (circRNA) in mouse and human hearts. However, the functional relevance of many of these abundantly expressed cardiomyocyte circRNA remains to be fully explored. Among the most abundant circRNA, one stems from the sodium-calcium exchanger gene, Slc8a1, exon 2 locus. Because of its very high abundance in cardiomyocytes we investigated the possible role of circSlc8a1 in the heart. METHODS AND RESULTS: We performed a miRNA screen using an array of 752 miRNAs with RNA recovered from a pull-down of endogenous cardiomyocyte circSlc8a1. MicroRNA-133a (miR-133a), with a prior well-recognized role in cardiac hypertrophy, was highly enriched in the fraction of circSlc8a1 pull-down (adjusted p-value < 0.001). We therefore followed-up validation of the functional interaction between circSlc8a1 and miR-133 using luciferase assays and reciprocal pull-down assays. In vivo, AAV9-mediated RNAi knockdown of circSlc8a1 attenuates cardiac hypertrophy from pressure-overload, whereas forced cardiomyocyte specific overexpression of circSlc8a1 resulted in heart failure. Molecular analyses showed targets of miR-133a including serum response factor (SRF), connective tissue growth factor (CTGF), adrenoceptor beta 1 (Adrb1) and adenylate cyclase 6 (Adcy6) to be regulated by circSlc8a1-directed intervention of knockdown and overexpression. CONCLUSION: In summary, circSlc8a1 can function as an endogenous sponge for miR-133a in cardiomyocytes. We propose that circSlc8a1 may serve as a novel therapeutic target for cardiac hypertrophy.
Source Title: Cardiovasc Res
URI: https://scholarbank.nus.edu.sg/handle/10635/155934
ISSN: 0008-6363
1755-3245
DOI: 10.1093/cvr/cvz130
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