Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3
发布时间 :2017-08-02
研究对象:Let-7f; 期刊:Neurochem Res; 影响因子:2.581; 合作单位:郑州大学第一附属医院、郑州大学基础医学院; 发表时间:2016年10月27日.

摘要

microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identiied let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dualcolor luorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke.


研究背景

microRNAs不仅在基因转录后调控中发挥重要作用,且也参与调控缺血性中风。在体内,miRNA let-7f的拮抗剂可以发挥神经保护作用,但脑缺血时let-7f发挥其作用的机制仍不清楚。研究发现,缺氧条件下,NDRG3可以通过激活Raf-ERK促进血管生成和细胞生长。本文旨在探究脑缺血时缺氧应答过程中let-7f调控NDRG3表达的机制。


方法流程

 


研究结果

1、(图1)。

 

                             图1 在原代培养的大鼠皮层神经元细胞中氧糖剥夺来诱导NDRG3表达


2、(图2)。

 

                                                             图2 pMCAO处理后大脑皮层NDRG3的表达情


3、(图3)。

 

                  

                                                     图3 let-7f抑制NDRG3的表达


4、(图4)。

 

                    图4 pMCAO处理后小鼠大脑皮层中let-7f抑制NDRG3的表达


伯信合作技术:FISH


参考文献

Yao Y, Wang W, Jing L, et al. Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3. Neurochem Res. 2017; 42(2):446-454.


原文链接:

10.1007/s11064-016-2091-x

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