MicroRNA-93 inhibits ischemia-reperfusion induced cardiomyocyte apoptosis by targeting PTEN.

MicroRNA-93 inhibits ischemia-reperfusion induced cardiomyocyte apoptosis by targeting PTEN.
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DOI:
10.18632/oncotarget.8941
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发表时间:
2016-05-17
期刊:
影响因子:
--
通讯作者:
Gao AM
Gao AM
中科院分区:
其他
文献类型:
--
作者:
Ke ZP;Xu P;Shi Y;Gao AM

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MicroRNAs参与了包括心肌缺血/再灌注(I/R)损伤在内的一些生物学和病理过程。最近的研究结果表明,miR-93可能对缺血性心脏病提供潜在的心脏保护作用。本研究旨在探讨miR-93在I/ r诱导的心肌细胞损伤中的作用及其可能的机制。在这项研究中,我们发现缺氧/再氧化(H/R)显著增加LDH释放、MDA含量、ROS生成和内质网应激(ERS)介导的心肌细胞凋亡,而与miR-93 mimic共转染可减弱这些凋亡。磷酸酶和紧张素同源物(PTEN)被确定为miR-93的靶基因。此外,miR-93 mimic在H/R下显著增加p-Akt水平,LY294002部分释放p-Akt。此外,Ad-miR-93在体内还能减轻心肌I/R损伤,表现为LDH和CK水平降低,梗死面积减少,细胞凋亡减少。综上所述,我们的研究结果表明miR-93可以通过抑制PI3K/AKT/PTEN信号传导来保护I/ r诱导的心肌细胞凋亡。
MicroRNAs have been implicated in some biological and pathological processes, including the myocardial ischemia/reperfusion (I/R) injury. Recent findings demonstrated that miR-93 might provide a potential cardioprotective effect on ischemic heart disease. This study was to investigate the role of miR-93 in I/R-induced cardiomyocyte injury and the potential mechanism. In this study, we found that hypoxia/reoxygenation (H/R) dramatically increased LDH release, MDA contents, ROS generation, and endoplasmic reticulum stress (ERS)-mediated cardiomyocyte apoptosis, which were attenuated by co-transfection with miR-93 mimic. Phosphatase and tensin homolog (PTEN) was identified as the target gene of miR-93. Furthermore, miR-93 mimic significantly increased p-Akt levels under H/R, which was partially released by LY294002. In addtion, Ad-miR-93 also attenuated myocardial I/R injury in vivo, manifested by reduced LDH and CK levels, infarct area and cell apoptosis. Taken together, our findings indicates that miR-93 could protect against I/R-induced cardiomyocyte apoptosis by inhibiting PI3K/AKT/PTEN signaling.
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