Hypoxia inducible mir-210 regulates normoxic gene expression involved in tumor initiation

By Xin Huang, L. Ding, K. Bennewith, R. Tong, K. Ang, Michael Story, Quynh-Thu Le, Amato J. Giaccia. Molecules and Cells, 2009

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Summary 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 & 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8dec4debe80d77dfd76e25b73937a332c8fdcccb