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.
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