Antitumor Activity of miR-1280 in Melanoma by Regulation of Src |
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Authors: | Vera Sun Wen B Zhou Mehdi Nosrati Shahana Majid Suresh Thummala David de Semir Vladimir Bezrookove Sebastien de Feraudy Liane Chun Dirk Schadendorf Robert Debs Mohammed Kashani-Sabet Altaf A Dar |
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Institution: | 1.Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco, California, USA;2.Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California, USA;3.Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Essen Hautklinik Huielandstraße, Essen, Germany |
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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. |
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