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

• Verfasst von: Luo, Chonglin [VerfasserIn]
• Verfasst von: Tetteh, Paul W. [VerfasserIn]
• Verfasst von: Merz, Patrick [VerfasserIn]
• Verfasst von: Dickes, Elke [VerfasserIn]
• Verfasst von: Abukiwan, Alia [VerfasserIn]
• Verfasst von: Hotz-Wagenblatt, Agnes [VerfasserIn]
• Verfasst von: Holland-Cunz, Stefan [VerfasserIn]
• Verfasst von: Sinnberg, Tobias [VerfasserIn]
• Verfasst von: Schittek, Birgit [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Verfasst von: Diederichs, Sven [VerfasserIn]
• Verfasst von: Eichmüller, Stefan B. [VerfasserIn]
• Titel: miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes
• Verf.angabe: 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
• Jahr: 2013
• Umfang: 8 S.
• Fussnoten: published online 15 November 2012 ; Gesehen am 08.06.2021
• Titel Quelle: Enthalten in: The journal of investigative dermatology
• Ort Quelle: Amsterdam : Elsevier, 1938
• Jahr Quelle: 2013
• Band/Heft Quelle: 133(2013), 3 vom: März, Seite 768-775
• ISSN Quelle: 1523-1747
• DOI: doi:10.1038/jid.2012.357
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1760066109

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.