MicroRNA-145-5p inhibits hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes by targeting ROCK1

被引:16
作者
Cheng, Chao [1 ]
Xu, Dong-Ling [1 ]
Liu, Xiao-Bo [2 ]
Bi, Shao-Jie [1 ]
Zhang, Juan [1 ]
机构
[1] Shandong Univ, Cheeloo Coll Med, Dept Cardiol, Hosp 2, 247 Beiyuan Rd, Jinan 250033, Shandong, Peoples R China
[2] Shandong Blood Ctr, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA-145-5p; ROCK1; hypoxia; reoxygenation; H9c2; cardiomyocyte apoptosis; ISCHEMIA-REPERFUSION INJURY; RHO-KINASE; CRUCIAL ROLE; ISCHEMIA/REPERFUSION; PROTECTS; HYPERTENSION; MIR-145; PLAYS; HEART; RNAS;
D O I
10.3892/etm.2021.10228
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
There is increasing evidence that microRNAs (miRs) play critical roles in the pathological and physiological processes associated with myocardial ischemia reperfusion (I/R). miR-145 has been extensively studied in the cardiovascular system; however, the role of miR-145 in myocardial I/R remains unclear. Therefore, the present study aimed to investigate the role and mechanism of miR-145-5p in myocardial I/R by establishing a hypoxia/reoxygenation (H/R) model using H9c2 cardiomyocytes. The expression of miR-145-5p was regulated by transfection and the potential target of miR-145-5p was identified. In addition, apoptosis of the cardiomyocytes was evaluated using flow cytometry and the detection of cleaved caspase-3 by western blotting. The results revealed that miR-145-5p expression was decreased while cell apoptosis and Rho-associated coiled-coil-containing kinase 1 (ROCK1) expression were increased in H/R-stimulated H9c2 cardiomyocytes. The upregulation of miR-145-5p reduced apoptosis and the expression of ROCK1 in H/R-stimulated H9c2 cardiomyocytes. Furthermore, the overexpression of ROCK1 significantly attenuated the miR-145-5p-induced reduction of apoptosis following H/R. In conclusion, the present study indicates that the overexpression of miR-145-5p inhibits H/R-induced cardiomyocyte apoptosis by targeting ROCK1.
引用
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页数:8
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共 35 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Long Noncoding RNAs From Clinical Genetics to Therapeutic Targets? [J].
Boon, Reinier A. ;
Jae, Nicolas ;
Holdt, Lesca ;
Dimmeler, Stefanie .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2016, 67 (10) :1214-1226
[3]   A Role for miR-145 in Pulmonary Arterial Hypertension Evidence From Mouse Models and Patient Samples [J].
Caruso, Paola ;
Dempsie, Yvonne ;
Stevens, Hannah C. ;
McDonald, Robert A. ;
Long, Lu ;
Lu, Ruifang ;
White, Kevin ;
Mair, Kirsty M. ;
McClure, John D. ;
Southwood, Mark ;
Upton, Paul ;
Xin, Mei ;
van Rooij, Eva ;
Olson, Eric N. ;
Morrell, Nicholas W. ;
MacLean, Margaret R. ;
Baker, Andrew H. .
CIRCULATION RESEARCH, 2012, 111 (03) :290-300
[4]   Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis [J].
Chang, Jiang ;
Xie, Min ;
Shah, Viraj R. ;
Schneider, Michael D. ;
Entman, Mark L. ;
Wei, Lei ;
Schwartz, Robert J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14495-14500
[5]   miR-145 and miR-143 regulate smooth muscle cell fate and plasticity [J].
Cordes, Kimberly R. ;
Sheehy, Neil T. ;
White, Mark P. ;
Berry, Emily C. ;
Morton, Sarah U. ;
Muth, Alecia N. ;
Lee, Ting-Hein ;
Miano, Joseph M. ;
Ivey, Kathryn N. ;
Srivastava, Deepak .
NATURE, 2009, 460 (7256) :705-U80
[6]   Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury JACC Review Topic of the Week [J].
Davidson, Sean M. ;
Ferdinandy, Peter ;
Andreadou, Ioanna ;
Botker, Hans Erik ;
Heusch, Gerd ;
Ibanez, Borja ;
Ovize, Michel ;
Schulz, Rainer ;
Yellon, Derek M. ;
Hausenloy, Derek J. ;
Garcia-Dorado, David .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2019, 73 (01) :89-99
[7]   A decade of caspases [J].
Degterev, A ;
Boyce, M ;
Yuan, JY .
ONCOGENE, 2003, 22 (53) :8543-8567
[8]   Lost in translation: miRNAs and mRNAs in ischemic preconditioning and ischemia/reperfusion injury [J].
Gottlieb, Roberta A. ;
Pourpirali, Somayeh .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2016, 95 :70-77
[9]   The Function of Rho-Associated Kinases ROCK1 and ROCK2 in the Pathogenesis of Cardiovascular Disease [J].
Hartmann, Svenja ;
Ridley, Anne J. ;
Lutz, Susanne .
FRONTIERS IN PHARMACOLOGY, 2015, 6
[10]   Myocardial ischemia-reperfusion injury: a neglected therapeutic target [J].
Hausenloy, Derek J. ;
Yellon, Derek M. .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (01) :92-100