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The MYCN oncogene is a direct target of miR-34a

Oncogene volume 27, pages 5204–5213 (2008)Cite this article

Abstract

Loss of 1p36 heterozygosity commonly occurs with MYCN amplification in neuroblastoma tumors, and both are associated with an aggressive phenotype. Database searches identified five microRNAs that map to the commonly deleted region of 1p36 and we hypothesized that the loss of one or more of these microRNAs contributes to the malignant phenotype of MYCN-amplified tumors. By bioinformatic analysis, we identified that three out of the five microRNAs target MYCN and of these miR-34a caused the most significant suppression of cell growth through increased apoptosis and decreased DNA synthesis in neuroblastoma cell lines with MYCN amplification. Quantitative RT–PCR showed that neuroblastoma tumors with 1p36 loss expressed lower level of miR-34a than those with normal copies of 1p36. Furthermore, we demonstrated that MYCN is a direct target of miR-34a. Finally, using a series of mRNA expression profiling experiments, we identified other potential direct targets of miR-34a, and pathway analysis demonstrated that miR-34a suppresses cell-cycle genes and induces several neural-related genes. This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma.

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Acknowledgements

We thank Dr Joon-Yong Chung and Xinyu Wen, MS for their excellent technical support. We also thank Dr John Maris, Dr Wendy London (Children's Oncology Group, Philadelphia, PA, USA) and Dr Steven Qualman (Cooperative Human Tissue Network, Columbus, OH, USA) for the NB tumor samples, and for invaluable discussion of this study with Dr John Maris and his group. This study is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government.

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Authors and Affiliations

  1. Oncogenomics Section, Pediatric Oncology Branch, Advanced Technology Center, National Cancer Institute, Gaithersburg, MD, USA

    J S Wei, Y K Song, S Durinck, Q-R Chen, A T C Cheuk, P Tsang, Q Zhang & J Khan

  2. The Advanced Biomedical Computing Center, National Cancer Institute-Frederick, SAIC-Frederick Inc., Frederick, MD, USA

    Q-R Chen

  3. Cell and Molecular Biology Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA

    C J Thiele

  4. Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA

    A Slack & J Shohet

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  1. J S Wei
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Correspondence to J Khan.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Wei, J., Song, Y., Durinck, S. et al. The MYCN oncogene is a direct target of miR-34a. Oncogene 27, 5204–5213 (2008). https://doi.org/10.1038/onc.2008.154

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