Abstract
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 language | English (US) |
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Pages (from-to) | 856-867 |
Number of pages | 12 |
Journal | Molecular cell |
Volume | 35 |
Issue number | 6 |
DOIs | |
State | Published - Sep 24 2009 |
Keywords
- CELLCYCLE
- RNA
- SIGNALING
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology