Abstract B20: miR-211 Functions as a metabolic switch in human melanoma cells

Abstract

Abstract The microRNA (miRNA) miR-211 negatively regulates genes that drive invasion of metastatic melanoma. Compared to normal human melanocytes, miR-211 expression is significantly reduced or absent in non-pigmented melanoma cells and lost during human melanoma progression. To investigate mechanisms of its tumor suppressor function, miR-211 was ectopically expressed in non-pigmented melanoma cells. Ectopic miR-211 expression destabilized hypoxia-inducible factor 1α (HIF-1α) and caused increased cell death during hypoxia. HIF-1α destabilization was correlated with down-regulation of a novel miR-211 target gene, pyruvate dehydrogenase kinase 4 (PDK4). We present evidence that resumption of miR-211 mediated down-regulation of PDK4 in melanoma cells caused hypoxia-induced cell death via HIF-1α destabilization. Thus the tumor suppressor miR-211 acts as a metabolic switch, and its loss is expected to promote cancer hallmarks in human melanomas. Citation Format: Joseph Mazar, Feng Qi, Bongyong Lee, John Marchica, Subramaniam Govindarajan, John Shelley, Jian-Liang Li, Animesh Ray, Ranjan J. Perera. miR-211 Functions as a metabolic switch in human melanoma cells. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B20.