Abstract
Wig-1 is a transcriptional target of the p53 tumor suppressor and encodes an mRNA stability-regulating protein. We show here that Wig-1 knockdown causes a dramatic inhibition of N-Myc expression and triggers differentiation in neuroblastoma cells carrying amplified N-Myc. Transient Wig-1 knockdown significantly delays development of N-Myc-driven tumors in mice. We also show that N-Myc expression is induced upon moderate p53-activating stress, suggesting a role of the p53-Wig-1-N-Myc axis in promoting cell cycle re-entry upon p53-induced cell cycle arrest and DNA repair. Moreover, our findings raise possibilities for the improved treatment of poor prognosis neuroblastomas that carry amplified N-Myc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carrier Proteins / antagonists & inhibitors
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Checkpoints
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Cell Line, Tumor
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DNA Repair
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Female
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HCT116 Cells
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Humans
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Mice
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Mice, Nude
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Neoplasms / pathology*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / metabolism*
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RNA Interference
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RNA, Messenger / metabolism*
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RNA, Small Interfering / metabolism
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RNA-Binding Proteins
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Transplantation, Heterologous
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Tumor Suppressor Protein p53 / metabolism
Substances
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Carrier Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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RNA, Small Interfering
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RNA-Binding Proteins
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Tumor Suppressor Protein p53
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ZMAT3 protein, human