Pulkkinen Kati, Malm Tarja, Turunen Mikko, Koistinaho Jari, Ylä-Herttuala Seppo
Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, FIN-70211 Kuopio, Finland.
FEBS Lett. 2008 Jul 9;582(16):2397-401. doi: 10.1016/j.febslet.2008.05.048. Epub 2008 Jun 6.
Shortage of oxygen is one of the prime stress conditions in tissues. In this study, we looked for microRNAs expressed during hypoxia and showed that miR-210 expression was upregulated in response to hypoxia in vitro and in vivo. An active form of the HIF-1alpha induced the expression of miR-210, showing the involvement of the HIF-1 signaling pathway in miR-210 gene transcription. Furthermore, miR-210 was shown to bind to the predicted target sites of ephrin-A3 or neuronal pentraxin 1, causing repression in luciferase reporter activity. Contrary to the microRNA-mediated repression hypothesis, ephrin-A3 was expressed at very high levels in post-ischemic mouse hippocampus in vivo. Thus, the regulatory effects of miR-210 on its targets in vivo need to be further characterized.
缺氧是组织中的主要应激条件之一。在本研究中，我们寻找了在缺氧期间表达的微小RNA，并表明miR-210的表达在体外和体内对缺氧均有上调。活性形式的HIF-1α诱导了miR-210的表达，表明HIF-1信号通路参与了miR-210基因转录。此外，miR-210被证明可与ephrin-A3或神经元五聚体蛋白1的预测靶位点结合，导致荧光素酶报告基因活性受到抑制。与微小RNA介导的抑制假说相反，ephrin-A3在体内缺血后小鼠海马体中表达水平非常高。因此，miR-210在体内对其靶标的调节作用需要进一步表征。
