miR-339-3p Is a Tumor Suppressor in Melanoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-06, Vol.76 (12), p.3562-3571
• Main Authors: Weber, Claudia E M, Luo, Chonglin, Hotz-Wagenblatt, Agnes, Gardyan, Adriane, Kordaß, Theresa, Holland-Letz, Tim, Osen, Wolfram, Eichmüller, Stefan B
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Genes, Tumor Suppressor - physiology; Melanoma - genetics; Melanoma - pathology; Melanoma - prevention & control; Mice; MicroRNAs - physiology; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Neoplasm Invasiveness
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-15-2932

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.