title: Antitumor activity of miR-1280 in melanoma by regulation of Src.
abstract: MicroRNAs (miRNAs) play a key role in cancer progression by coordinately repressing target genes involved in cell proliferation, migration, and invasion. miRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of complementary mRNA. Here, we report that expression of miR-1280 is significantly suppressed in human melanoma specimens when compared with nevi, and in human melanoma cell lines when compared with cultured normal human melanocytes. The proto-oncogene Src was identified as a target of miR-1280 action. Levels of Src expression were significantly higher in melanoma samples and cell lines than in nevi and normal melanocytes. miR-1280 overexpression significantly suppressed the luciferase activity of reporter plasmids containing the full-length 3' untranslated region of Src. miR-1280-mediated suppression of Src led to substantial decreases in melanoma cell proliferation, cell cycle progression, invasion, as well as induced melanoma cell apoptosis. The effects of miR-1280 overexpression on melanoma cell proliferation and growth were reversed by Src overexpression. Intratumoral delivery of miR-1280 significantly suppressed melanoma cell growth in vivo. Our results demonstrate a novel role for miR-1280 as a tumor suppressor in melanoma, identify the Src signaling pathway as a target of miR-1280 action, and suggest a potential therapeutic role for miR-1280 in melanoma.
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Sun
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Wen B
authors.initials: WB
authors.lastname: Zhou
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nosrati
authors.affiliation: Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA.
authors.forename: Shahana
authors.initials: S
authors.lastname: Majid
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Thummala
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: de Semir
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bezrookove
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: de Feraudy
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Liane
authors.initials: L
authors.lastname: Chun
authors.affiliation: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Essen Hautklinik Huielandstraße, Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Debs
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kashani-Sabet
authors.affiliation: Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA.
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Dar
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C000715470:MAS1 protein, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D008156:Luciferases; D016392:Proto-Oncogene Proteins pp60(c-src)