%0 Journal Article
%T Circular RNA-circLRP6 protects cardiomyocyte from hypoxia-induced apoptosis by facilitating hnRNPM-mediated expression of FGF-9.
%A Ding W
%A Ding L
%A Lu Y
%A Sun W
%A Wang Y
%A Wang J
%A Gao Y
%A Li M
%J FEBS J
%V 291
%N 6
%D 2024 Mar 17
%M 38105623
%F 5.622
%R 10.1111/febs.17038
%X Coronary atherosclerosis-induced myocardial ischemia leads to cardiomyocyte apoptosis. The regulatory mechanisms for cardiomyocyte apoptosis have not been fully understood. Circular RNAs are non-coding RNAs which play important roles in heart function maintenance and progression of heart diseases by regulating gene transcription and protein translation. Here, we reported a conserved cardiac circular RNA, which is generated from the second exon of LRP6 and named circLRP62-2 . CircLRP62-2 can protect cardiomyocyte from hypoxia-induced apoptosis. The expression of circLRP62-2 in cardiomyocytes was down-regulated under hypoxia, while forced expression of circLRP62-2 inhibited cell apoptosis. Normally, circLRP62-2 was mainly localized in the nucleus. Under hypoxia, circLRP62-2 is associated with heterogeneous nuclear ribonucleoprotein M (hnRNPM) to be translocated into the cytoplasm. It recruited hnRNPM to fibroblast growth factor 9 (FGF9) mRNA to enhance the expression of FGF9 protein, promoting hypoxia-adaption and viability of cardiomyocytes. In summary, this study uncovers a new inhibitor of apoptosis and reveals a novel anti-apoptotic pathway composed of circLRP62-2 , hnRNPM, and FGF9, which may provide therapeutic targets for coronary heart disease and ischemic myocardial injury.