Abstract
Abstract Recent our work shed light on the critical roles of RUNX3 in early tumorigenesis. Hypoxia has been reported to be an early tumorigenic insult. Previously, we showed that RUNX3 is silenced by G9a HMT under hypoxia. However, the possible direct modification of RUNX3 by G9a induced by hypoxia and its outcome are not yet investigated. Here we show that RUNX3 physically interacts with G9a. Under hypoxic conditions, G9a directly methylates lysines 129 and 171 of RUNX3. G9a-methylated RUNX3 is localized to the cytoplasm and degrade through Smurf-mediated ubiquitination pathway. Hypoxia and G9a overexpression decreased RUNX3-responsive genes by DNA microarray analysis. Consistently, tumor suppressive role of RUNX3 was decreased by G9a-mediated methylation in gastric cancer xenograft model. Taken together, our results demonstrate that methylation by G9a is a key chemical modification for the regulation of RUNX3 tumor suppressor function in hypoxic conditions and in early tumorigenic stage. Citation Format: You Mie Lee. Hypoxia-induced G9a histone methyltransferase is crucial for blunting RUNX3 tumor suppressor function. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2193. doi:10.1158/1538-7445.AM2015-2193
Published Version
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