miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1

Ronit Cohen, Eyal Greenberg, Yael Nemlich, Jacob Schachter, Gal Markel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)19006-19016
Number of pages11
JournalOncotarget
Volume6
Issue number22
DOIs
StatePublished - 2015

Keywords

  • ETV1
  • Melanoma
  • Motility
  • miR-17
  • microRNAs (miRNAs)

Fingerprint

Dive into the research topics of 'miR-17 regulates melanoma cell motility by inhibiting the translation of ETV1'. Together they form a unique fingerprint.

Cite this