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

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 wit...

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Hauptverfasser: Luo, Chonglin (VerfasserIn) , Tetteh, Paul W. (VerfasserIn) , Merz, Patrick (VerfasserIn) , Dickes, Elke (VerfasserIn) , Abukiwan, Alia (VerfasserIn) , Hotz-Wagenblatt, Agnes (VerfasserIn) , Holland-Cunz, Stefan (VerfasserIn) , Sinnberg, Tobias (VerfasserIn) , Schittek, Birgit (VerfasserIn) , Schadendorf, Dirk (VerfasserIn) , Diederichs, Sven (VerfasserIn) , Eichmüller, Stefan B. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2013
In: The journal of investigative dermatology
Year: 2013, Jahrgang: 133, Heft: 3, Pages: 768-775
ISSN:1523-1747
DOI:10.1038/jid.2012.357
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/jid.2012.357
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022202X15361613
Volltext
Verfasserangaben:Chonglin Luo, Paul W. Tetteh, Patrick R. Merz, Elke Dickes, Alia Abukiwan, Agnes Hotz-Wagenblatt, Stefan Holland-Cunz, Tobias Sinnberg, Birgit Schittek, Dirk Schadendorf, Sven Diederichs and Stefan B. Eichmüller

MARC

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520 |a 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. 
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