A MicroRNA Signature of Hypoxia† (cid:1)

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, accession number A- MEXP-258), which contains 381 probes for mature and precursor human microRNAs and 393 probes for mouse microRNAs, together with controls. There are four spot replicates for each probe on the chip. Hybridization signals were detected by biotin binding of a Streptavidin-Alexa 647 conjugate using a GenePix 4000B scanner (Axon Instruments). Images were quantified using the

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