p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance
نویسندگان
چکیده
Neuroblastoma is the most common extra-cranial solid tumor of childhood. Despite significant advances, it currently still remains one of the most difficult childhood cancers to cure, with less than 40% of patients with high-risk disease being long-term survivors. MYCN is a proto-oncogene implicated to be directly involved in neuroblastoma development. Amplification of MYCN is associated with rapid tumor progression and poor prognosis. Novel therapeutic strategies which can improve the survival rates whilst reducing the toxicity in these patients are therefore required. Here we discuss genes regulated by MYCN in neuroblastoma, with particular reference to p53, SKP2, and DKK3 and strategies that may be employed to target them.
منابع مشابه
MYCN-regulated miRNA-92 inhibits secretion of the tumor suppressor DICKKOPF-3 (DKK3) in neuroblastoma.
The MYCN oncogene is frequently amplified in neuroblastoma. It is one of the most consistent markers of bad prognosis for this disease. Dickkopf-3 (DKK3) is a secreted protein of the DKK family of Wnt regulators. It functions as a tumor suppressor in a range of cancers, including neuroblastoma. MYCN was recently found to downregulate DKK3 mRNA. In this study, we show that MYCN knockdown in MYCN...
متن کاملDickkopf-3 is regulated by the MYCN-induced miR-17-92 cluster in neuroblastoma.
Neuroblastoma (NB) is a paediatric tumour with a remarkable diverse clinical behaviour. Approximately half of the high stage aggressive tumours are characterized by MYCN gene amplification but our understanding of the role of MYCN in NB oncogenesis is incomplete. Previous studies have shown that MYCN expression is inversely correlated with expression of Dickkopf-3 (DKK3), a gene encoding an ext...
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Neuroblastoma is a pediatric tumor which can spontaneously regress or differentiate into a benign tumor. MYCN oncogene amplification occurs in 22% of neuroblastomas and is associated with poor prognosis. Retinoic acid (RA), a molecule able to induce differentiation and to decrease MYCN expression, is used in the therapy of neuroblastomas. The neuropeptide vasoactive intestinal peptide (VIP) is ...
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PURPOSE Amplified MYCN oncogene defines a subgroup of neuroblastomas with poor outcome. However, a substantial number of MYCN single-copy neuroblastomas exhibits an aggressive phenotype similar to that of MYCN-amplified neuroblastomas even in the absence of high MYCN mRNA and/or protein levels. EXPERIMENTAL DESIGN To identify shared molecular mechanisms that mediate the aggressive phenotype i...
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