MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene
MiR-124 protects human hepatic L02 cells from H2O2-induced apoptosis by targeting Rab38 gene
复制标题
MiR-124 通过靶向 Rab38 基因保护人肝 L02 细胞免受 H2O2 诱导的细胞凋亡。
DOI：
10.1016/j.bbrc.2014.05.085
复制
发表时间：
2014-07-18
影响因子：
3.1
通讯作者：
Yang, Yang
中科院分区：
文献类型：
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作者：
Li, Xiaohua;Yi, Shuhong;Yang, Yang
背景：肝脏缺血再灌注损伤（IRI）是肝脏外科医生不可避免的临床问题。由于microRNAs （miRNAs）参与肝脏多种病理生理过程，本研究旨在探讨miR-124在肝脏IRI中的作用及其潜在机制。方法：建立大鼠肝脏IRI模型。使用微阵列检测mirna的差异表达，并通过qRT-PCR检测miR-124的表达。建立过氧化氢（H2O2）诱导氧化应激细胞凋亡模型。流式细胞术检测细胞凋亡，CCK8检测细胞活力。采用Western blotting和qRT-PCR检测Rab38的表达，采用荧光素酶报告基因法验证miR-124靶基因的表达。结果：大鼠肝脏IRI后miRNA谱发生显著变化，miR-124在肝脏IRI后明显下调。MiR-124通过上调AKT通路的激活，减少h2o2诱导的人肝L02细胞凋亡。Rab38是miR-124的靶基因，参与h2o2诱导的细胞凋亡。干扰Rab38基因的表达可以通过增加AKT的磷酸化来保护h2o2诱导的肝细胞凋亡。miR-124的这些保护作用因Rab38的过表达而减弱。结论：许多mirna参与大鼠肝脏IRI， miR-124在该模型中显著降低。MiR-124通过靶向Rab38基因，激活AKT通路，显著降低h2o2诱导的人肝L02细胞凋亡。(C) 2014爱思唯尔公司版权所有。
Background: Hepatic ischemia reperfusion injury (IRI) is an inevitable clinical problem for liver surgeons. Because microRNAs (miRNAs) participate in various hepatic pathophysiological processes, this study aimed to explore the role and potential mechanism of miR-124 in hepatic IRI.Methods: A liver IRI model was established in rats. The differential expression of miRNAs was detected using microarrays, and the expression of miR-124 was measured by qRT-PCR. A hydrogen peroxide (H2O2)-induced oxidative stress apoptosis model was also established. Cell apoptosis was detected by flow cytometry, and viability was detected by CCK8. The expression of Rab38 was detected by Western blotting and qRT-PCR, and a luciferase reporter assay was used to verify the expression of the miR-124 target gene.Results: The miRNA spectrum changes dramatically after hepatic IRI in rats, and miR-124 is significantly down-regulated after liver IRI. MiR-124 decreases the H2O2-induced apoptosis of human hepatic L02 cells by up-regulating the activation of the AKT pathway. Rab38 is a target gene of miR-124 and is involved in H2O2-induced apoptosis. Interference with the expression of the Rab38 gene can protect hepatic L02 from H2O2-induced apoptosis by increasing the phosphorylation of AKT. These protective effects of miR-124 are attenuated by over-expression of Rab38.Conclusions: Many miRNAs are involved in hepatic IRI in rats, and miR-124 is significantly decreased in this model. MiR-124 significantly decreases the H2O2-induced apoptosis of human hepatic L02 cells by targeting the Rab38 gene and activating the AKT pathway. (C) 2014 Elsevier Inc. All rights reserved.