title: miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.
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.
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: s.eichmueller@dkfz.de.
authors.forename: Chonglin
authors.initials: C
authors.lastname: Luo
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Tetteh
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Merz
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Dickes
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Alia
authors.initials: A
authors.lastname: Abukiwan
authors.affiliation: Genomics and Proteomics Core Facility, Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Hotz-Wagenblatt
authors.affiliation: Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Holland-Cunz
authors.affiliation: Department of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sinnberg
authors.affiliation: Department of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: Department of Dermatology, University Hospital Essen, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Helmholtz-University-Group 'Molecular RNA Biology & Cancer', German Cancer Research Center (DKFZ) and Institute of Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Diederichs
authors.affiliation: Division of Translational Immunology (D015), German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: c.luo@dkfz.de.
authors.forename: Stefan B
authors.initials: SB
authors.lastname: Eichmüller
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D000071221:Enhancer of Zeste Homolog 2 Protein; D006801:Humans; D008545:Melanoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D009857:Oncogenes / Q000235:genetics / Q000502:physiology*; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C545567:MIRN137 microRNA, human; C497234:MITF protein, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D019859:Proto-Oncogene Proteins c-met