Cardiac Hypertrophy is Positively Regulated by MicroRNA‑24 in Rats

• Published in: Chinese medical journal Vol. 131; no. 11; pp. 1333 - 1341
• Main Authors: Gao, Juan, Zhu, Min, Liu, Rui-Feng, Zhang, Jian-Shu, Xu, Ming
• Format: Journal Article
• Language: English
• Published: China Key Laboratory of Molecular Cardiovascular Science, Ministry of Education 05.06.2018; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Cardiac Hypertrophy; Cell Cycle; MicroRNA; MicroRNA-24; p27; Original; MicroRNA; Cell Cycle; p27; Cardiac Hypertrophy; MicroRNA-24
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.232793

MicroRNA-24 (miR-24) plays an important role in heart failure by reducing the efficiency of myocardial excitation-contraction coupling. Prolonged cardiac hypertrophy may lead to heart failure, but little is known about the role of miR-24 in cardiac hypertrophy. This study aimed to preliminarily investigate the function of miR-24 and its mechanisms in cardiac hypertrophy. Twelve Sprague-Dawley rats with a body weight of 50 ± 5 g were recruited and randomly divided into two groups: a transverse aortic constriction (TAC) group and a sham surgery group. Hypertrophy index was measured and calculated by echocardiography and hematoxylin and eosin staining. TargetScans algorithm-based prediction was used to search for the targets of miR-24, which was subsequently confirmed by a real-time polymerase chain reaction and luciferase assay. Immunofluorescence labeling was used to measure the cell surface area, and H-leucine incorporation was used to detect the synthesis of total protein in neonatal rat cardiac myocytes (NRCMs) with the overexpression of miR-24. In addition, flow cytometry was performed to observe the alteration in the cell cycle. Statistical analysis was carried out with GraphPad Prism v5.0 and SPSS 19.0. A two-sided P < 0.05 was considered as the threshold for significance. The expression of miR-24 was abnormally increased in TAC rat cardiac tissue (t = -2.938, P < 0.05). TargetScans algorithm-based prediction demonstrated that CDKN1B (p27, Kip1), a cell cycle regulator, was a putative target of miR-24, and was confirmed by luciferase assay. The expression of p27 was decreased in TAC rat cardiac tissue (t = 2.896, P < 0.05). The overexpression of miR-24 in NRCMs led to the decreased expression of p27 (t = 4.400, P < 0.01), and decreased G0/G1 arrest in cell cycle and cardiomyocyte hypertrophy. MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.