Cardiac Hypertrophy is Positively Regulated by MicroRNA‑24 in Rats

Overview

Journal Chin Med J (Engl)

Specialty General Medicine

Date 2018 May 23

PMID 29786048

Citations 7

Authors

Juan Gao

Min Zhu

Rui-Feng Liu

Jian-Shu Zhang

Ming Xu

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: MiR-24 promotes cardiac hypertrophy partly by affecting the cell cycle through down-regulation of p27 expression.

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References

Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A . A mammalian microRNA expression atlas based on small RNA library sequencing. Cell. 2007; 129(7):1401-14. PMC: 2681231. DOI: 10.1016/j.cell.2007.04.040. View

Wang J, Liew O, Richards A, Chen Y . Overview of MicroRNAs in Cardiac Hypertrophy, Fibrosis, and Apoptosis. Int J Mol Sci. 2016; 17(5). PMC: 4881570. DOI: 10.3390/ijms17050749. View

Kiraz H, Poyraz F, Kip G, Erdem O, Alkan M, Arslan M . The effect of levosimendan on myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats. Libyan J Med. 2015; 10(1):29269. PMC: 4673913. DOI: 10.3402/ljm.v10.29269. View

Li R, Tao J, Guo Y, Wu H, Liu R, Bai Y . In vivo suppression of microRNA-24 prevents the transition toward decompensated hypertrophy in aortic-constricted mice. Circ Res. 2013; 112(4):601-5. PMC: 3622206. DOI: 10.1161/CIRCRESAHA.112.300806. View

Wang Z, Smith K, Murphy M, Piloto O, Somervaille T, Cleary M . Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature. 2008; 455(7217):1205-9. PMC: 4084721. DOI: 10.1038/nature07284. View

Wang D, Zhai G, Ji Y, Jing H . microRNA-10a Targets T-box 5 to Inhibit the Development of Cardiac Hypertrophy. Int Heart J. 2017; 58(1):100-106. DOI: 10.1536/ihj.16-020. View

Van Rooij E, Sutherland L, Liu N, Williams A, McAnally J, Gerard R . A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure. Proc Natl Acad Sci U S A. 2006; 103(48):18255-60. PMC: 1838739. DOI: 10.1073/pnas.0608791103. View

Chu I, Hengst L, Slingerland J . The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer. 2008; 8(4):253-67. DOI: 10.1038/nrc2347. View

Haeusler A, Donnelly C, Periz G, Simko E, Shaw P, Kim M . C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature. 2014; 507(7491):195-200. PMC: 4046618. DOI: 10.1038/nature13124. View

10.

Heggermont W, Papageorgiou A, Quaegebeur A, Deckx S, Carai P, Verhesen W . Inhibition of MicroRNA-146a and Overexpression of Its Target Dihydrolipoyl Succinyltransferase Protect Against Pressure Overload-Induced Cardiac Hypertrophy and Dysfunction. Circulation. 2017; 136(8):747-761. DOI: 10.1161/CIRCULATIONAHA.116.024171. View

11.

Muller M, Kuiperij H, Claassen J, Kusters B, Verbeek M . MicroRNAs in Alzheimer's disease: differential expression in hippocampus and cell-free cerebrospinal fluid. Neurobiol Aging. 2013; 35(1):152-8. DOI: 10.1016/j.neurobiolaging.2013.07.005. View

12.

Li J, Zhang C, Xing Y, Janicki J, Yamamoto M, Wang X . Up-regulation of p27(kip1) contributes to Nrf2-mediated protection against angiotensin II-induced cardiac hypertrophy. Cardiovasc Res. 2011; 90(2):315-24. DOI: 10.1093/cvr/cvr010. View

13.

Yano K, Grove J, Reed D, Chun H . Determinants of the prognosis after a first myocardial infarction in a migrant Japanese population. The Honolulu Heart Program. Circulation. 1993; 88(6):2582-95. DOI: 10.1161/01.cir.88.6.2582. View

14.

Yuan Y, Zhang Y, Han X, Li Y, Zhao X, Sheng L . Relaxin alleviates TGFβ1-induced cardiac fibrosis via inhibition of Stat3-dependent autophagy. Biochem Biophys Res Commun. 2017; 493(4):1601-1607. DOI: 10.1016/j.bbrc.2017.09.110. View

15.

Lee R, Ambros V . An extensive class of small RNAs in Caenorhabditis elegans. Science. 2001; 294(5543):862-4. DOI: 10.1126/science.1065329. View

16.

Bicknell K, Coxon C, Brooks G . Can the cardiomyocyte cell cycle be reprogrammed?. J Mol Cell Cardiol. 2007; 42(4):706-21. DOI: 10.1016/j.yjmcc.2007.01.006. View

17.

Liu X, Wang A, Heidbreder C, Jiang L, Yu J, Kolokythas A . MicroRNA-24 targeting RNA-binding protein DND1 in tongue squamous cell carcinoma. FEBS Lett. 2010; 584(18):4115-20. PMC: 2964934. DOI: 10.1016/j.febslet.2010.08.040. View

18.

Zhao C, Ma X, Guo H, Li P, Liu H . RIP2 deficiency attenuates cardiac hypertrophy, inflammation and fibrosis in pressure overload induced mice. Biochem Biophys Res Commun. 2017; 493(2):1151-1158. DOI: 10.1016/j.bbrc.2017.07.035. View

19.

Xiang Y, Cheng J, Wang D, Hu X, Xie Y, Stitham J . Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor. Blood. 2015; 125(22):3377-87. PMC: 4447857. DOI: 10.1182/blood-2015-01-620278. View

20.

Maclellan W, Schneider M . Genetic dissection of cardiac growth control pathways. Annu Rev Physiol. 2000; 62:289-319. DOI: 10.1146/annurev.physiol.62.1.289. View