TY - JOUR AU - Weber, Claudia E M AU - Luo, Chonglin AU - Hotz-Wagenblatt, Agnes AU - Gardyan, Adriane AU - Kordaß, Theresa AU - Holland-Letz, Tim AU - Osen, Wolfram AU - Eichmüller, Stefan TI - miR-339-3p Is a Tumor Suppressor in Melanoma. JO - Cancer research VL - 76 IS - 12 SN - 1538-7445 CY - Philadelphia, Pa. PB - AACR M1 - DKFZ-2017-05906 SP - 3562 - 3571 PY - 2016 AB - 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. KW - MIRN-339 microRNA, mouse (NLM Chemicals) KW - Mcl1 protein, mouse (NLM Chemicals) KW - MicroRNAs (NLM Chemicals) KW - Myeloid Cell Leukemia Sequence 1 Protein (NLM Chemicals) LB - PUB:(DE-HGF)16 C6 - pmid:27197185 DO - DOI:10.1158/0008-5472.CAN-15-2932 UR - https://inrepo02.dkfz.de/record/130828 ER -