title: miR-211 and MITF modulation by Bcl-2 protein in melanoma cells.
abstract: Melanoma, the most lethal form of skin cancer, is frequently associated with alterations in several genes, among which the Bcl-2 oncogene plays an important role in progression, chemosensitivity and angiogenesis. Also microRNA (miRNA) are emerging as modulators of melanoma development and progression, and among them, miR-211, located within the melastatin-1/TRPM1 (transient receptor potential cation channel, subfamily M, member 1 protein) gene, is prevalently expressed in the melanocyte lineage and acts as oncosuppressor. Using several human melanoma cell lines and their Bcl-2 stably overexpressing derivatives, we evaluated whether there was a correlation between expression of Bcl-2 and miR-211. Western blot analysis and quantitative real-time polymerase chain reaction demonstrated reduced expression of pri-miR-211, miR-211, TRPM1, and MLANA levels, after Bcl-2 overexpression, associated with increased expression of well-known miR-211 target genes. Overexpression of mature miR-211 in Bcl-2 overexpressing cells rescued Bcl-2 ability to increase cell migration. A decreased nuclear localization of microphthalmia-associated transcription factor (MITF), a co-regulator of both miR-211 and TRPM1, and a reduced MITF recruitment at the TRPM1 and MLANA promoters were also evidenced in Bcl-2 overexpressing cells by immunofluorescence and chromatin immunoprecipitation experiments, respectively. Reduction of Bcl-2 expression by small interference RNA confirmed the ability of Bcl-2 to modulate miR-211 and TRPM1 expression. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: De Luca
authors.affiliation: Molecular Oncogenesis Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pelosi
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Trisciuoglio
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: D'Aguanno
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Desideri
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Farini
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Martile
authors.affiliation: Laboratory of Cutaneous Physiopathology, San Gallicano Dermatologic Institute, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bellei
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Tupone
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Candiloro
authors.affiliation: Molecular Oncogenesis Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Regazzo
authors.affiliation: Molecular Oncogenesis Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Rizzo
authors.affiliation: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Del Bufalo
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C549405:MIRN211 microRNA, human; C497234:MITF protein, human; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D019253:Proto-Oncogene Proteins c-bcl-2
keywords: Bcl-2; melanoma; microRNA