miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1
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Ronit Cohen1,2,*, Eyal Greenberg1,2,*, Yael Nemlich1,2, Jacob Schachter1,**, Gal Markel1,2,3,**
1Ella Institute of Melanoma Research, Sheba Medical Center, Ramat-Gan, Israel
2Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
3Talpiot Medical Leadership Program, Sheba Medical Center, Ramat-Gan, Israel
*These authors have contributed equally to this work
**These authors have contributed equally to this work
Gal Markel, e-mail: firstname.lastname@example.org
Keywords: melanoma, microRNAs (miRNAs), miR-17, ETV1, motility
Received: April 21, 2015 Accepted: May 20, 2015 Published: June 01, 2015
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.
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