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Previous studies have suggested that the HIF transcription factors can both activate and inhibit gene expression. Here we show that HIF1 regulates the expression of mir-210 in a variety of tumor types through a hypoxia-responsive element. Expression analysis in primary head and neck tumor samples indicates that mir-210 may serve as an in vivo marker for tumor hypoxia. By Argonaute protein immunoprecipitation, we identified 50 potential mir-210 targets and validated randomly selected ones. The majority of these 50 genes are not classical hypoxia-inducible genes, suggesting mir-210 represses genes expressed under normoxia that are no longer necessary to adapt and survive in a hypoxic environment. When human head and neck or pancreatic tumor cells ectopically expressing mir-210 were implanted into immunodeficient mice, mir-210 repressed initiation of tumor growth. Taken together, these data implicate an important role for mir-210 in regulating the hypoxic response of tumor cells and tumor growth.

Original publication

DOI

10.1016/j.molcel.2009.09.006

Type

Journal article

Journal

Mol Cell

Publication Date

24/09/2009

Volume

35

Pages

856 - 867

Keywords

Animals, Base Sequence, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Cell Transformation, Neoplastic, Eukaryotic Initiation Factor-2, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Silencing, Head and Neck Neoplasms, Homeodomain Proteins, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Immunoprecipitation, Male, Mice, Mice, Nude, MicroRNAs, Molecular Sequence Data, Neoplasm Transplantation, Oligonucleotide Array Sequence Analysis, Pancreatic Neoplasms, Protein Binding, Receptor, Fibroblast Growth Factor, Type 5, Reproducibility of Results, Response Elements, Stress, Physiological, Time Factors, Transcription Factors, Transcription, Genetic, Transduction, Genetic, Up-Regulation