Abstract 978: microRNA-211 modulates energy metabolism in human melanoma cells by destabilizing HIF1-α and downregulating PDK4

Abstract

Abstract MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in cellular physiology and tumorigenesis. We have previously reported that the expression of the melanocyte-specific miRNA miR-211 is significantly reduced or absent in non-pigmented melanoma cells and clinical melanoma samples. Here we report that ectopic expression of miR-211 in non-pigmented melanoma cells increases mitochondrial number, NADP to NADPH ratio, oxygen consumption, and fatty acid synthesis. Ectopic expression of miR-211 destabilizes hypoxia inducible factor 1α (HIF-1α) and downregulates pyruvate dehydrogenase kinase 4 (PDK4), which is known to convert cellular pyruvate to acetyl co-enzyme A. miR-211-expressing cells were characterized by uptake of glutamine, rather than glucose, as a source of cellular energy. Global proteomic, transcriptomic, lipidomic, and metabolomic profiling with integrated analysis revealed that miR-211 modulates several “-omics” signatures associated with oxidative phosphorylation. Here we show for the first time that a microRNA and its target genes play a key role in regulating mitochondrial energy metabolism in melanomas. Citation Format: Joseph Mazar, Adam Richardson, Feng Qi, Bongyong Lee, Angeles Duran, Subramaniam Govindarajan, John Shelley, Laurence M. Brill, Jian-Liang Li, Xianlin Han, Jorge Moscat, Ranjan Joseph Perera. microRNA-211 modulates energy metabolism in human melanoma cells by destabilizing HIF1-α and downregulating PDK4. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 978. doi:10.1158/1538-7445.AM2014-978