Antitumor Activity of miR-1280 in Melanoma by Regulation of Src

作者：Sun, Vera; Zhou, Wen B.; Nosrati, Mehdi; Majid, Shahana; Thummala, Suresh; de Semir, David; Bezrookove, Vladimir; de Feraudy, Sebastien; Chun, Liane; Schadendorf, Dirk; Debs, Robert; Kashani-Sabet, Mohammed; Dar, Altaf A.^*

来源：Molecular Therapy, 2015, 23(1): 71-78.

DOI：10.1038/mt.2014.176

• PANCREATIC ADENOCARCINOMA CELLS
• HUMAN CANCER-CELLS
• IN-VIVO
• KINASE INHIBITOR
• ACTIVATION
• EXPRESSION
• MICRORNA
• PROTOONCOGENE
• METASTASIS
• GROWTH

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.

• 出版日期2015-1