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


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.

SUBMITTER: Huang X 

PROVIDER: S-EPMC2782615 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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

Huang Xin X   Ding Lianghao L   Bennewith Kevin L KL   Tong Ricky T RT   Welford Scott M SM   Ang K Kian KK   Story Michael M   Le Quynh-Thu QT   Giaccia Amato J AJ  

Molecular cell 20090901 6


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 ma  ...[more]

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