miR-29b affects neurocyte apoptosis by targeting MCL-1 during cerebral ischemia/reperfusion injury.
miR-29b affects neurocyte apoptosis by targeting MCL-1 during cerebral ischemia/reperfusion injury.
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DOI：
10.3892/etm.2018.6622
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发表时间：
2018-10
影响因子：
2.7
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Huang Z;Lu L;Jiang T;Zhang S;Shen Y;Zheng Z;Zhao A;Gao R;Li R;Zhou S;Liu J
本研究旨在确定miRNA（miR）-29b抑制剂是否在体外对脑缺血/再灌注（I/R）损伤具有保护作用并探讨其潜在机制。作为诱导性脑IR损伤的模型，将N2 a细胞暴露于氧-葡萄糖剥夺/复氧（OGD/R）环境。使用该模型，证明了与正常环境中的细胞相比，miR-29 b显著上调。然后使用双荧光素酶分析研究了miR-29 b和髓细胞白血病序列（MCL）-1之间的相互作用，揭示了通过3′非翻译区对MCL-1的强烈调控。使用OGD/R模型，本研究另外分别使用Cell Counting kit 8和流式细胞术测定来检查miR-29 b和miR-29 b抑制剂对细胞活力和凋亡的影响。miR-29 b转染导致N2 a细胞凋亡增加，并在OGD/R环境下降低细胞活力。然而，这种作用被miR-29 b抑制剂逆转。最后，检测了miR-29 b对几种Wnt相关蛋白表达的影响。观察到B细胞淋巴瘤-2被miR-29 B抑制，MCL-1也是如此，而caspase-3表达被促进。miR-29 b抑制剂表现出相反的效果。总体而言，miR-29 b在脑I/R损伤期间通过靶向MCL-1促进神经细胞凋亡。本研究的结果提示了一个潜在的新的治疗缺血性卒中的治疗靶点。
The present study aimed to determine whether an miRNA (miR)-29b inhibitor protected against cerebral ischemia/reperfusion (I/R) injury in vitro and to investigate the underlying mechanisms. As a model for induced cerebral IR injury, N2a cells were exposed to an oxygen-glucose deprivation/reoxygenation (OGD/R) environment. Using this model, it was demonstrated that miR-29b was significantly upregulated compared with cells in a normal environment. The interactions between miR-29b and myeloid cell leukemia sequence (MCL)-1 were then investigated using dual-luciferase assays, revealing a strong regulation of MCL-1 through the 3′untranslated region. Using the OGD/R model, the present study additionally examined the effects of miR-29b and miR-29b inhibitor on cell viability and apoptosis using Cell Counting kit 8 and flow cytometry assays, respectively. miR-29b transfection led to increased N2a cell apoptosis and reduced cell viability under an OGD/R environment. However, this effect was reversed by the miR-29b inhibitor. Finally, the effects of miR-29b on the expression of several Wnt-associating proteins were examined. It was observed that B cell lymphoma-2 was inhibited by miR-29b, as was MCL-1, whereas caspase-3 expression was promoted. The miR-29b inhibitor demonstrated the opposite effect. Overall, miR-29b promoted neurocyte apoptosis by targeting MCL-1 during cerebral I/R injury. The results of the present study suggest a potential novel therapeutic target for the treatment of ischemic stroke.
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DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
DOI：
10.1111/febs.13944
发表时间：
2016-12
期刊：
The FEBS journal
影响因子：
--
作者：
Annis RP;Swahari V;Nakamura A;Xie AX;Hammond SM;Deshmukh M
通讯作者：
Deshmukh M
影响因子：
3.7
作者：
De Gasperi R;Graham ZA;Harlow LM;Bauman WA;Qin W;Cardozo CP
通讯作者：
Cardozo CP
影响因子：
8
作者：
Mott, J. L.;Kobayashi, S.;Gores, G. J.
通讯作者：
Gores, G. J.
影响因子：
1.9
作者：
Altintas, Ozge;Altintas, Mehmet Ozgen;Asil, Talip
通讯作者：
Asil, Talip