Abstract
To metastasize, a tumor cell must acquire abilities such as the capacity to colonize new tissue and evade immune surveillance. Recent evidence suggests that microRNAs can promote the evolution of malignant behaviors by regulating multiple targets. We performed a microRNA analysis of human melanoma, a highly invasive cancer, and found that miR-30b/30d upregulation correlates with stage, metastatic potential, shorter time to recurrence, and reduced overall survival. Ectopic expression of miR-30b/30d promoted the metastatic behavior of melanoma cells by directly targeting the GalNAc transferase GALNT7, resulted in increased synthesis of the immunosuppressive cytokine IL-10, and reduced immune cell activation and recruitment. These data support a key role of miR-30b/30d and GalNAc transferases in metastasis, by simultaneously promoting cellular invasion and immunosuppression.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Cell Proliferation
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Disease Progression
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Gene Expression Regulation, Neoplastic
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Gene Silencing
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Genome, Human / genetics
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Humans
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Immune Tolerance / genetics*
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Interleukin-10 / metabolism
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Melanoma / enzymology
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Melanoma / genetics
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Melanoma / pathology
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Mice
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Molecular Sequence Data
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N-Acetylgalactosaminyltransferases / antagonists & inhibitors
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N-Acetylgalactosaminyltransferases / genetics
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N-Acetylgalactosaminyltransferases / metabolism*
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Neoplasm Invasiveness
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Neoplasm Metastasis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Polypeptide N-acetylgalactosaminyltransferase
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Polysaccharides / metabolism
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Up-Regulation
Substances
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MIRN130 microRNA, human
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MIRN30b microRNA, human
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MicroRNAs
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Neoplasm Proteins
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Polysaccharides
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Interleukin-10
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N-Acetylgalactosaminyltransferases