Human Gene Set: WEI_MYCN_TARGETS_WITH_E_BOX


Standard name WEI_MYCN_TARGETS_WITH_E_BOX
Systematic name M12113
Brief description Genes whose promoters contain E-box motifs and whose expression changed in MYCN-3 cells (neuroblastoma) upon induction of MYCN [GeneID=4613].
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18504438   Authors: Wei JS,Song YK,Durinck S,Chen QR,Cheuk AT,Tsang P,Zhang Q,Thiele CJ,Slack A,Shohet J,Khan J
Exact source Table 4S
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform Human_NCBI_Gene_ID
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Version history 3.0: First introduced

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