Hypoxia-Inducible mir-210 Regulates Normoxic Gene Expression Involved in Tumor Initiation

Xin Huang, Lianghao Ding, Kevin L. Bennewith, Ricky T. Tong, Scott M. Welford, K. Kian Ang, Michael Story, Quynh Thu Le, Amato J. Giaccia

Research output: Contribution to journalArticle

418 Scopus citations

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 languageEnglish (US)
Pages (from-to)856-867
Number of pages12
JournalMolecular Cell
Volume35
Issue number6
DOIs
StatePublished - Sep 24 2009
Externally publishedYes

Keywords

  • CELLCYCLE
  • RNA
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Huang, X., Ding, L., Bennewith, K. L., Tong, R. T., Welford, S. M., Ang, K. K., Story, M., Le, Q. T., & Giaccia, A. J. (2009). Hypoxia-Inducible mir-210 Regulates Normoxic Gene Expression Involved in Tumor Initiation. Molecular Cell, 35(6), 856-867. https://doi.org/10.1016/j.molcel.2009.09.006