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Therapeutics, Targets, and Chemical Biology

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

Claudia E.M. Weber, Chonglin Luo, Agnes Hotz-Wagenblatt, Adriane Gardyan, Theresa Kordaß, Tim Holland-Letz, Wolfram Osen and Stefan B. Eichmüller
Claudia E.M. Weber
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Chonglin Luo
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Agnes Hotz-Wagenblatt
2Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Adriane Gardyan
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Theresa Kordaß
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Tim Holland-Letz
3Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Wolfram Osen
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Stefan B. Eichmüller
1GMP and T-Cell Therapy Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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  • For correspondence: s.eichmueller@dkfz.de
DOI: 10.1158/0008-5472.CAN-15-2932 Published June 2016
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Abstract

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.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received October 27, 2015.
  • Revision received April 8, 2016.
  • Accepted April 8, 2016.
  • ©2016 American Association for Cancer Research.
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Cancer Research: 76 (12)
June 2016
Volume 76, Issue 12
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miR-339-3p Is a Tumor Suppressor in Melanoma
Claudia E.M. Weber, Chonglin Luo, Agnes Hotz-Wagenblatt, Adriane Gardyan, Theresa Kordaß, Tim Holland-Letz, Wolfram Osen and Stefan B. Eichmüller
Cancer Res June 15 2016 (76) (12) 3562-3571; DOI: 10.1158/0008-5472.CAN-15-2932

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miR-339-3p Is a Tumor Suppressor in Melanoma
Claudia E.M. Weber, Chonglin Luo, Agnes Hotz-Wagenblatt, Adriane Gardyan, Theresa Kordaß, Tim Holland-Letz, Wolfram Osen and Stefan B. Eichmüller
Cancer Res June 15 2016 (76) (12) 3562-3571; DOI: 10.1158/0008-5472.CAN-15-2932
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