Abstract 2020: MiR-210 modulates the hypoxic response in endothelial and ovarian cancer cells

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Tumor growth and progression is intricately linked to hypoxia induced adaptive changes. Hypoxia is known to alter chemosensitivity, upregulation of putative cancer initiating stem cells and the microenvironment. The multitude of these changes is brought about by differential gene expression. Hypoxia inducible transcription factor-1 alpha (HIF-α) is a key transducer of altered gene expression under low oxygen or ischemia. In addition to the transcriptional activation of multiple genes, hypoxia also alters miRNA levels in tumor and vascular endothelial cells. miRNAs are small noncoding RNAs ∼22 nucleotides in length representing 1%-2% of the eukaryotic transcriptome. We used microarrays to determine relative changes in 467 miRNAs in endothelial and MA148 ovarian cancer cells exposed to hypoxia. One of the miRNAs, miR-210 was significantly up-regulated under hypoxia by microarray analysis (2-fold, P <0.01). miR-210 expression changes were validated by RT-qPCR. Exogenous over expression of miR-210 in endothelial cells increased their proliferative capacity and induced angiogenesis. These effects were reversed by morpholino antagomiR specific for miR-210. In-vivo studies using transgenic zebrafish showed that miR-210 can increase angiogenesis which could be readily reversed by morpholino antagomiR. These studied together showed that miR-210 plays an important role in angiognenesis. We then over-expressed miR-210 in ovarian cancer cells. While in vitro growth rate was not altered, over expression of miR-210 changed the kinetics of tumor growth. Taken together, these data implicate an important role for mir-210 in hypoxia induced adaptive changes in tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2020.