Abstract A65: MicroRNA miR‐210 modulates cellular response to hypoxia through the MYC antagonist MNT

Intratumoral hypoxia is well known as a hallmark of most solid tumors. Here, we studied expression level of about 200 microRNAs in a panel of cancer cell lines from different tissues, and identified a microRNA miR210, its expression was prominently up‐regulated by hypoxia. Over expression of miR210 in cancer cell lines partially reversed the hypoxic gene expression signature and allowed cells to escape from hypoxia‐induced cell‐cycle arrest. We then identified MNT, a known MYC antagonist, as a key miR‐210 target. miR‐210 directly down‐regulated MNT transcript and protein via recognition sites in the transcript 3′ UTR. Consistent with a role for MNT as a miR‐210 target, RNA interference‐mediated knockdown of MNT phenocopied miR‐210 over expression cell cycle effect. Furthermore, loss of MYC abolished the ability of miR‐210 to override hypoxia‐induced cell‐cycle arrest. Thus, miR‐210 could function as a modulator in cancer cells in response to hypoxic conditions through Myc network. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A65.