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Hsa_circ_0010729 regulates H2O2-induced myocardial injury by regulating miR-1184/RIPK1 axis
Institution:1. Department of Geriatrics, The Second Affiliated Hospital of Hainan Medical University, No.48, Baishuitang Road, Haikou, Hainan Province 571000, China;2. Department of Cardiology, Qionghai Hospital of Traditional Chinese Medicine, Qionghai City, Hainan Province 571400, China;1. Histotomorphometry and stereology research center, Shiraz University of Medical Sciences, Shiraz, Iran;2. Tissue engineering lab, Anatomy Department, Shiraz University of Medical Sciences, Shiraz, Iran;1. Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India;2. Nephrology & Renal Transplant, Jaypee Hospital, Noida, Delhi NCR, India;3. Urology & Renal Transplant, Jaypee Hospital, Noida, Delhi NCR, India;1. Department of Biology, Faculty of Art and Sciences, Tekirdağ Namık Kemal University, Tekirdağ, Turkey;2. Department of Medical Genetics, School of Medicine, University of Marmara, İstanbul, Turkey;3. Department of Gynecology and Obstetrics, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey;4. Department of General Surgery, Faculty of Medicine, Sağlık Bilimleri University, İstanbul, Turkey;5. Department of General Surgery, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Turkey;6. Department of Nutrition and Dietetics, School of Health, Tekirdağ Namık Kemal University, Tekirdağ, Turkey
Abstract:BackgroundIschemia-reperfusion (I/R) is an important risk factor for cardiovascular diseases (CVDs) and cardiac transplantation, as I/R can cause myocardial cell hypoxia/reoxygenation (H/R) injury. Recent research has shown that circular RNAs (circRNAs) may affect the progress of H/R-induced myocardial injury, but the mechanism remains unknown. Our work explored the role of circ_0010729 in H2O2-induced myocardial injury.MethodsThe levels of circ_0010729, microRNA-1184 (miR-1184) and mRNA of receptor interacting serine/threonine kinase 1 (RIPK1) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in human cardiac myocytes (HCMs). Meanwhile, the protein level of RIPK1 was quantified by western blot analysis. Besides, the cell functions were examined by 5-Ethynyl-29-deoxyuridine (EdU) assay, flow cytometry assay, western blot and antioxidant indexes analysis. Furthermore, the interplay between miR-1184 and circ_0010729 or RIPK1 was detected by dual-luciferase reporter assay. Eventually, the in vivo experiments were applied to measure the role of circ_0010729.ResultsThe levels of circ_0010729 RNA and RIPK1 protein were increased, and the miR-1184 was decreased in HCMs exposed to H2O2. In functional analysis, circ_0010729 deficiency restrained cell apoptosis and oxidative stress, whereas promoted cell proliferation in HCMs under H2O2 exposure. Moreover, miR-1184 inhibited the H2O2-induced myocardial injury by targeting RIPK1. Mechanistically, circ_0010729 acted as a miR-1184 sponge to regulate the level of RIPK1.ConclusionCirc_0010729 promotes H2O2-induced myocardial injury, and thus circ_001729 may be targeted as a potential therapy for H/R-induced myocardial injury.
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