基因敲除
CTGF公司
压力过载
肌肉肥大
生物
心肌细胞
钠钙交换剂
细胞生物学
RNA干扰
小RNA
环状RNA
内科学
核糖核酸
内分泌学
生长因子
医学
基因
遗传学
心肌肥大
受体
细胞内
作者
T.B. Lim,Edita Aliwarga,Tuan Danh Anh Luu,Yiqing Peter Li,Shi Ling Ng,Annadoray Lavenniah,Stephanie Sian,Matthew Ackers‐Johnson,Roger Foo
出处
期刊:Cardiovascular Research
[Oxford University Press]
日期:2019-05-22
卷期号:115 (14): 1998-2007
被引量:116
摘要
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.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.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.
科研通智能强力驱动
Strongly Powered by AbleSci AI