Hypoxia induces microRNA miR-210 in vitro and in vivo: Ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210

Pulkkinen, Kati; Malm, Tarja; Turunen, Mikko; Koistinaho, Jari; Ylä-Herttuala, Seppo

doi:10.1016/j.febslet.2008.05.048

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Volume 582, Issue 16 , Pages 2397-2401, 9 July 2008

Hypoxia induces microRNA miR-210 in vitro and in vivo:

Ephrin-A3 and neuronal pentraxin 1 are potentially regulated by miR-210

Edited by Ulrike Kutay

Kati Pulkkinen
- Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, FIN-70211 Kuopio, Finland
Tarja Malm
- Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, Kuopio, Finland
Mikko Turunen
- Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, FIN-70211 Kuopio, Finland
Jari Koistinaho
- Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, Kuopio, Finland
Seppo Ylä-Herttuala
- Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, Kuopio University, P.O. Box 1627, FIN-70211 Kuopio, Finland
- Department of Medicine, Kuopio University, Kuopio, Finland
- Gene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
- Corresponding author. Present address: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. Fax: +358 17 163751.

Received 26 March 2008; received in revised form 29 May 2008; accepted 29 May 2008. published online 06 June 2008.

Abstract

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-1α 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.

Keywords: MicroRNA, Hypoxia, Ephrin-A3, Neuronal pentraxin 1