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Abstract
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.
SUPPLEMENTAL MATERIAL
This work was supported by NIH grant P30 DK-34928 and an AACR/PanCan career development award to M.I.; a Kimmel Scholar award to G.A.C.; grants from the Italian Ministry of Public Health, the Italian Association for Cancer Research (AIRC), and Comitato Sostenitori Progetto CAN-2006 to M.N.; and grants from the National Cancer Institute to C.M.C. M.F. is a recipient of a fellowship from Fondazione Italiana per la Ricerca sul Cancro (FIRC).
We declare that we have no competing financial interests.