title: miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1.
abstract: Melanoma is an aggressive malignancy with a high metastatic potential. microRNA-17 (miR-17) is a member of the oncogenic miR-17/92 cluster. Here we study the effect of miR-17 on melanoma cell motility. Over expression of the mature or pri-microRNA form of miR-17 in WM-266-4 and 624mel melanoma lines enhances cell motility, evident in both wound healing and transwell migration assays. TargetScan algorithm predicts the PEA3-subfamily member ETV1 as a direct target of miR-17. Indeed, a 3-4-fold decrease of ETV1 protein levels are observed following miR-17 transfection into the various melanoma lines, with no significant change in ETV1 mRNA expression. Dual luciferase experiments demonstrate direct binding of miR-17 to the 3'-untranslated region of ETV1, confirmed by abolishing point mutations in the putative binding site. These combined results suggest regulation of ETV1 by miR-17 by a direct translational repression. Further, in both melanoma cell lines ETV1 knockdown by selective siRNA successfully pheno-copies the facilitated cell migration, while overexpression of ETV1 inhibits cell motility and migration. Altered ETV1 expression does not affect melanoma net-proliferation. In conclusion, we show a new role for miR-17 in melanoma, facilitating cell motility, by targeting the translation of ETV1 protein, which may support the development of metastasis.
authors.affiliation: Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel.|Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Cohen
authors.affiliation: Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel.|Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Greenberg
authors.affiliation: Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel.|Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Nemlich
authors.affiliation: Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Schachter
authors.affiliation: Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel.|Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.|Talpiot Medical Leadership Program, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D014176:Protein Biosynthesis; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
keywords: ETV1; melanoma; miR-17; microRNAs (miRNAs); motility