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Molecular and Cellular Biology, March 2007, p. 1859-1867, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A MicroRNA Signature of Hypoxia{dagger} ,{triangledown}

Ritu Kulshreshtha,1 Manuela Ferracin,2 Sylwia E. Wojcik,3 Ramiro Garzon,3 Hansjuerg Alder,3 Francisco J. Agosto-Perez,3 Ramana Davuluri,3 Chang-Gong Liu,3 Carlo M. Croce,3 Massimo Negrini,2 George A. Calin,3 and Mircea Ivan1*

Molecular Oncology Research Institute, Tufts-New England Medical Center, Boston, Massachusetts 02111,1 Department of Experimental and Diagnostic Medicine and Interdepartmental Center for Cancer Research, University of Ferrara, Ferrara 44100, Italy,2 Comprehensive Cancer Center, Ohio State University, Columbus, Ohio 432103

Received 28 July 2006/ Returned for modification 28 August 2006/ Accepted 10 December 2006

Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.

* Corresponding author. Mailing address: 750 Washington Street, Box 5609, Boston, MA 02111. Phone: (617) 636-7514. Fax: (617) 636-6127. E-mail: mivan{at}tufts-nemc.org.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{triangledown} Published ahead of print on 28 December 2006.

Molecular and Cellular Biology, March 2007, p. 1859-1867, Vol. 27, No. 5
0270-7306/07/$08.00+0     doi:10.1128/MCB.01395-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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