circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p

Frontiers in Cardiovascular Medicine

Haoyuan Zheng¹  Mingxiao Hou²  Lin Shi³  Changci Tong³  Yunen Liu⁴ 

[1] Laboratory of Rescue Center of Severe Wound and Trauma Chinese People's Liberation Army, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command of China Medical University, Shenyang, China;Laboratory of Rescue Center of Severe Wound and Trauma Chinese People's Liberation Army, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command of China Medical University, Shenyang, China;The Second Affiliated Hospital of Shenyang Medical College, The Veterans General Hospital of Liaoning Province, Shenyang, China;Shenyang Medical College, Shenyang, China;Laboratory of Rescue Center of Severe Wound and Trauma Chinese People's Liberation Army, Emergency Medicine Department of General Hospital of Northern Theater Command, Shenyang, China;The Second Affiliated Hospital of Shenyang Medical College, The Veterans General Hospital of Liaoning Province, Shenyang, China;Shenyang Medical College, Shenyang, China;

关键词: heart failure;    RNA;    untranslated;    computational biology;    ferroptosis;   

DOI  :  10.3389/fcvm.2021.656093

来源: Frontiers

【 摘 要 】

Circular RNA (circRNA) is a subclass of non-coding RNAs that enables the circular transcripts resistant to the exonuclease digestion. Iron homeostasis is essential for the body to maintain normal physiological functions. At present, the relationship among circRNA, iron metabolism and heart failure remains largely unknown. This study aimed to explore the regulatory mechanism of circRNA and iron metabolism in heart failure. We obtained circRNA, miRNA and mRNA data from public databases and built a ceRNA network. The prediction results were verified in the myocardial tissues of pressure overload-induced heart failure mice through the use of histopathological staining methods, iron and malondialdehyde (MDA) measurement tests, quantitative real-time PCR (qRT-PCR), Western blot analysis and luciferase reporter assay. A total of 4 genes related to iron metabolism and oxidative stress were identified, and a ceRNA network involving 7 circRNAs, 7 miRNAs, and 4 mRNAs was constructed using bioinformatics tools. The results of qRT-PCR and Western blot analyses indicated that the expression level of FTH1 was similar with that predicted by bioinformatics analysis. Echocardiographic measurement showed that heart failure mice have lower fractional shortening and ejection fraction. Moreover, the myocardium of heart failure mice displayed obvious fibrosis as well as increased levels of iron and MDA compared to control mice. Besides, circSnx12 could act as an endogenous sponge to bind with miR-224-5p, and the 3'UTR region of FTH1 also had miRNA binding sites. A circRNA-miRNA-mRNA regulatory network was successfully constructed by identifying differentially expressed genes related to iron metabolism. This new approach reveals potential circRNA targets for the treatment of heart failure.

【 授权许可】

CC BY