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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Down-Regulation / genetics
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Down-Regulation / physiology*
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Enhancer of Zeste Homolog 2 Protein
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Humans
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Melanoma / metabolism
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Melanoma / mortality
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Melanoma / pathology*
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Microphthalmia-Associated Transcription Factor / genetics
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Microphthalmia-Associated Transcription Factor / metabolism
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Neoplasm Invasiveness / pathology*
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Neoplasm Staging
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Oncogenes / genetics
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Oncogenes / physiology*
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Polycomb Repressive Complex 2 / genetics
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Polycomb Repressive Complex 2 / metabolism
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Proto-Oncogene Proteins c-met / genetics
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Proto-Oncogene Proteins c-met / metabolism
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RNA, Small Interfering / pharmacology
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Skin Neoplasms / metabolism
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Skin Neoplasms / mortality
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Skin Neoplasms / pathology*
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Survival Rate
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Y-Box-Binding Protein 1 / genetics
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Y-Box-Binding Protein 1 / metabolism
Substances
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MIRN137 microRNA, human
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MITF protein, human
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MicroRNAs
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Microphthalmia-Associated Transcription Factor
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RNA, Small Interfering
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Y-Box-Binding Protein 1
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YBX1 protein, human
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Proto-Oncogene Proteins c-met