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Wig-1, a novel regulator of N-Myc mRNA and N-Myc-driven tumor growth.

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.

SUBMITTER: Vilborg A

PROVIDER: S-EPMC3358011 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Wig-1, a novel regulator of N-Myc mRNA and N-Myc-driven tumor growth.

Vilborg A A Bersani C C Wickström M M Segerström L L Kogner P P Wiman K G KG

Cell death & disease 20120419

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 prom ...[more]

PMID: 22513872

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