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Journal of Shanghai University >

2019 , Vol. 25 >Issue 1: 10 - 17

DOI: https://doi.org/10.12066/j.issn.1007-2861.2097

Precision and Translational Medicine

Role of miR-19b in protecting cardiomyocytes from apoptosis by activating Akt signaling

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  • 1. Department of Cardiology, Anting Hospital,Shanghai 201805, China
    2. Department of Cardiology, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, China

Received date: 2018-10-26

  Online published: 2019-02-26

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Abstract

[Objective] The purpose of the research is to investigate the effects of miR-19b on apoptosis and its underlying mechanisms in the oxygen glucose deprivation/reperfusion (OGD/R) model of neonatal rat cardiomyocytes (NRCMs). [Methods] NRCMs are obtained from neonatal rats by enzymatic hydrolysis and then transfected by miR-19b mimics and miR-19b inhibitor for the following study. A model of OGD/R has been built in NRCMs to mimic myocardial ischemia and reperfusion injury (MIRI). Terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP)-biotion nick end labeling (TUNEL) assay has been performed to detect cardiomyocyte apoptosis. Western blot has been applied for detecting the expression of apoptotic proteins (Bcl2, Bax and Caspase3) and the downstream proteins of miR-19b. TUNEL staining indicates that miR-19b mimics could reduce the ratio of TUNEL positive nucleus to total nucleus and miR-19b inhibitor has opposite effects. [Results] Results based on western blot support the observations above. Moreover, miR-19b mimics could down-regulate the expression of phosphatase and tensin homolog (PTEN) and activate Akt signaling while miR-19b inhibitor has opposite effects. The rescue experiment has confirmed that PTEN-siRNA could reverse the promotion of miR-19b inhibitor on cardiomyocyte apoptosis. [Conclusion] miR-19b may protect cardiomyocytes from apoptosis through the activation of Akt signaling via regulating PTEN negatively.

Key words： cardiomyocytes apoptosis; miR-19b; Akt signaling

Cite this article

ZHU Hongwen, YU Pujiao, XU Jiahong . Role of miR-19b in protecting cardiomyocytes from apoptosis by activating Akt signaling[J]. Journal of Shanghai University, 2019 , 25(1) : 10 -17 . DOI: 10.12066/j.issn.1007-2861.2097

References

[1] Hausenloy D J, Yellon D M . Myocardial ischemia-reperfusion injury: a neglected therapeutic target[J]. J Clin Invest, 2013,123(1):92-100.
[2] Jennings R B, Sommers H M, Smyth G A , et al. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog[J]. Arch Pathol, 1960,70:68-78.
[3] Diaz I, Smani T . New insights into the mechanisms underlying vascular and cardiac effects of urocortin[J]. Curr Vasc Pharmacol, 2013,11(4):457-464.
[4] Cash J L, Bena S, Headland S E , et al. Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23[J]. EMBO Rep, 2013,14(11):999-1007.
[5] Zhu L, Wei T, Gao J , et al. The cardioprotective effect of salidroside against myocardial ischemia reperfusion injury in rats by inhibiting apoptosis and inflammation[J]. Apoptosis, 2015,20(11):1433-1443.
[6] Chouchani E T, Pell V R, Gaude E , et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS[J]. Nature, 2014,515(7527):431-435.
[7] Ibanez B, Heusch G, Ovize M , et al. Evolving therapies for myocardial ischemia/reperfusion injury[J]. J Am Coll Cardiol, 2015,65(14):1454-1471.
[8] Li B, Li R, Zhang C , et al. microRNA-7a/b protects against cardiac myocyte injury in ischemia/reperfusion by targeting poly(ADP-ribose) polymerase[J]. PLoS One, 2014, DOI: 10.1371/journal.pone.0090096.
[9] Yu S, Li G . MicroRNA expression and function in cardiac ischemic injury[J]. J Cardiovasc Transl Res, 2010,3(3):241-245.
[10] Yang Q, Yang K, Li A . microRNA-21 protects against ischemia-reperfusion and hypoxia-reperfusion-induced cardiocyte apoptosis via the phosphatase and tensin homolog/Akt-dependent mechanism[J]. Mol Med Rep, 2014,9(6):2213-2220.
[11] Fuziwara C S, Kimura E T . Insights into regulation of the miR-17-92 cluster of miRNAs in cancer[J]. Front Med (Lausanne), 2015,2:64.
[12] Chen J, Huang Z P, Seok H Y , et al. miR-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts[J]. Circ Res, 2013,112(12):1557-1566.
[13] Liu M, Yang R, Urrehman U , et al. miR-19b suppresses PTPRG to promote breast tumorigenesis[J]. Oncotarget, 2016,7(39):64100-64108.
[14] Xie D, Yuan P, Wang D , et al. Effects of naringin on the expression of miR-19b and cell apoptosis in human hepatocellular carcinoma[J]. Oncol Lett, 2017,14(2):1455-1459.
[15] Xue Y, Wei Z, Ding H , et al. microRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1alpha in the progression of atherosclerosis[J]. Atherosclerosis, 2015,241(2):671-681.
[16] Zhong C, Wang K, Liu Y , et al. miR-19b controls cardiac fibroblast proliferation and migration[J]. J Cell Mol Med, 2016,20(6):1191-1197.
[17] 胡晓山, 余章斌, 李萌萌 , 等. miR-19b 转基因小鼠的构建及表型分析[J]. 南京医科大学学报(自然科学版), 2013,33(5):579-585.
[18] Mavrakis K J, van der Meulen J, Wolfe A L , et al. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL)[J]. Nat Genet, 2011,43(7):673-678.
[19] Wang M H, Lin C L, Zhang J J , et al. Role of PTEN in cholera toxin-induced SWO38 glioma cell differentiation[J]. Mol Med Rep, 2013,7(6):1912-1918.
[20] Manning B D, Toker A . AKT/PKB signaling: navigating the network[J]. Cell, 2017,169(3):381-405.
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