Differential microRNA profiling in a cellular hypoxia reoxygenation model upon posthypoxic propofol treatment reveals alterations in autophagy signaling network.
Differential microRNA profiling in a cellular hypoxia reoxygenation model upon posthypoxic propofol treatment reveals alterations in autophagy signaling network.
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缺氧后丙泊酚治疗后细胞缺氧复氧模型中的差异 microRNA 分析揭示了自噬信号网络的变化。
DOI：
10.1155/2013/378484
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发表时间：
2013
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Chen Z;Hu Z;Lu Z;Cai S;Gu X;Zhuang H;Ruan Z;Xia Z;Irwin MG;Feng D;Zhang L
近年来的研究表明，异丙酚可能通过抑制缺氧/复氧（H/R）引起的过量活性氧引起的细胞自噬性死亡而发挥细胞保护作用。研究表明，在异丙酚缺氧后处理（P-PostH）的存在或不存在下，包括自噬相关基因在内的基因表达模式在H/R过程中发生显著变化。然而，造成这种差异的原因在很大程度上仍不清楚。microRNA为基因调控提供了一种新的机制。在本研究中，我们系统地分析了microRNA表达的变化，使用人脐静脉内皮细胞（HUVECs）进行H/R在存在或不存在的posthypopolysis异丙酚治疗。然后使用microRNA微阵列进行microRNA的全基因组分析。14个miRNAs差异表达，其中6个通过定量实时PCR（Q-PCR）验证，其中3个显著增加，而1个减少。为了获得关于改变的miRNA的后续调控的无偏见的全局视角，使用基因本体论（GO）分析来分析十种miRNA的预测靶标以构建信号传导网络。有趣的是，已知鉴定出的六种microRNA靶向自噬相关基因。总之，我们的研究结果表明，不同的miRNA表达模式诱导异丙酚缺氧处理在H/R和miRNA表达模式的改变涉及调节独特的自噬相关基因的表达。
Recent studies indicate that propofol may protect cells via suppressing autophagic cell death caused by excessive reactive oxygen species induced by hypoxia reoxygenation (H/R). It is established that gene expression patterns including autophagy-related genes changed significantly during the process of H/R in the presence or absence of propofol posthypoxia treatment (P-PostH). The reasons for such differences, however, remain largely unknown. MicroRNAs provide a novel mechanism for gene regulation. In the present study, we systematically analyzed the alterations in microRNA expression using human umbilical vein endothelial cells (HUVECs) subjected to H/R in the presence or absence of posthypoxic propofol treatment. Genome-wide profiling of microRNAs was then conducted using microRNA microarray. Fourteen miRNAs are differentially expressed and six of them were validated by the quantitative real-time PCR (Q-PCR) of which three were substantially increased, whereas one was decreased. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, predicted targets of ten miRNAs were analyzed using the Gene Ontology (GO) analysis to build signaling networks. Interestingly, six of the identified microRNAs are known to target autophagy-related genes. In conclusion, our results revealed that different miRNA expression patterns are induced by propofol posthypoxia treatment in H/R and the alterations in miRNA expression patterns are implicated in regulating distinctive autophagy-related gene expression.
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