title: miR-339-3p Is a Tumor Suppressor in Melanoma.
abstract: Determinants of invasion and metastasis in cancer remain of great interest to define. Here, we report the definition of miR-339-3p as a novel tumor suppressive microRNA that blocks melanoma cell invasion without affecting cell survival. miR-339-3p was identified by a comprehensive functional screen of a human miRNA mimetic library in a cell-based assay for invasion by the melanoma cell line A375. miR-339-3p was determined as a strong inhibitor of invasion differentially expressed in melanoma cells and healthy melanocytes. MCL1 was defined as a target for downregulation by miR-339-3p, functioning through direct interaction with the 3' untranslated region of MCL1 mRNA. Blocking miR-339-3p by an antagomiR was sufficient to increase melanoma cell invasion, an effect that could be phenocopied by RNAi-mediated silencing of MCL1. In vivo studies established that miR-339-3p overexpression was sufficient to decrease lung colonization by A375 melanoma cells in NSG mice, relative to control cells. Overall, our results defined miR-339-3p as a melanoma tumor suppressor, the levels of which contributes to invasive aggressiveness. Cancer Res; 76(12); 3562-71. ©2016 AACR.
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Claudia E M
authors.initials: CE
authors.lastname: Weber
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Chonglin
authors.initials: C
authors.lastname: Luo
authors.affiliation: Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Adriane
authors.initials: A
authors.lastname: Gardyan
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Kordaß
authors.affiliation: Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Holland-Letz
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Osen
authors.affiliation: GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. s.eichmueller@dkfz.de.
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Eichmüller
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D009361:Neoplasm Invasiveness
chemical_list: C000614039:MIRN-339 microRNA, mouse; C579094:Mcl1 protein, mouse; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein