Micro-RNA deletion in neuroblastoma: A possible alternative mechanism of MYCN overexpression

Autor:	T. Reshef-Ronen, Y. Goshen, Batia Stark, Shifra Ash, J. Nordenberg, I. Yaniv, Smadar Avigad, M. Jeison
Rok vydání:	2006
Předmět:	chemistry.chemical_classification Genetics Cancer Research Mechanism (biology) Biology medicine.disease Protein expression Cell biology Oncology chemistry Neuroblastoma microRNA medicine Nucleotide Gene
Zdroj:	Journal of Clinical Oncology. 24:9052-9052
ISSN:	1527-7755 0732-183X
DOI:	10.1200/jco.2006.24.18_suppl.9052
Popis:	9052 Background: Micro-RNAs (miRNAs) are small noncoding RNAs of 18 to 25 nucleotides that regulate protein expression. The biological functions of miRNAs are not yet fully understood. miRNA genes were recently found to be abnormally expressed in several types of cancer. By negatively regulating proto-oncogenes, miRNAs could act as tumor suppressors and conversely, by inhibiting tumor suppressors function as oncogenes. Neuroblastoma (NB) is the most common solid tumor in children under 5 years of age. Major adverse prognostic factors include: age over 1 year, advanced stages, adrenal primary site, MYCN amplification, diploid or tetraploid DNA content (DI), and chromosomal aberrations - including 1p deletions. We studied a possible involvement of miRNAs in neuroblastoma. Methods: The cohort consisted of 72 patients: 65% of them were above 1 year of age, 72% with advanced stages, 33% of the patients progressed. Median follow up was 60 months (ranging 1–221). Genomic DNA from 72 tumors were analyzed for the presence of 7 miRNAs located on chromosome 1p, ranging from 1p36.33 to 1p31.1 by PCR. Results: Deletion of one or more of the miRNAs was identified in 50% of the tumors.The most prevalent deletions were of two miRNAs: miR 30e located on 1p34.2 (29%) and miR 34a on 1p 36.23 (22%), accounting for 40% of the patients with a deletion of one or both of these miRs. Interestingly, miR 30e and miR 34a are known to negatively regulate the oncogene MYCN. MYCN protein expression is currently being evaluated in this cohort. Conclusions: The deletions of these miRNAs in neuroblastoma tumors suggest their involvement as tumor suppressor genes. This implies a new mechanism for the overexpression of MYCN. Discovery of the miRNAs and their targets involved in neuroblastoma has a therapeutic potential, for the development of new targeted therapies. No significant financial relationships to disclose.
Databáze:	OpenAIRE
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