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J Invest Dermatol. 2013 Mar;133(3):768-775. doi: 10.1038/jid.2012.357. Epub 2012 Nov 15.

miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

Author information

1
Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: s.eichmueller@dkfz.de.
2
Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Genomics and Proteomics Core Facility, Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
5
Department of Dermatology, University of Tübingen, Tübingen, Germany.
6
Department of Dermatology, University Hospital Essen, Essen, Germany.
7
Helmholtz-University-Group 'Molecular RNA Biology & Cancer', German Cancer Research Center (DKFZ) and Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
8
Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: c.luo@dkfz.de.

Abstract

MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

PMID:
23151846
DOI:
10.1038/jid.2012.357
[Indexed for MEDLINE]
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