NCYM is upregulated by lncUSMycN and modulates N-Myc expression

Liu,Pei Y.; Atmadibrata,Bernard; Mondal,Sujanna; Tee,Andrew E.; Liu,Tao

doi:10.3892/ijo.2016.3730

NCYM is upregulated by lncUSMycN and modulates N-Myc expression

Authors:
- Pei Y. Liu
- Bernard Atmadibrata
- Sujanna Mondal
- Andrew E. Tee
- Tao Liu
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Affiliations: Children's Cancer Institute Australia for Medical Research, Randwick, Sydney, NSW 2031, Australia
Published online on: October 12, 2016 https://doi.org/10.3892/ijo.2016.3730
Pages: 2464-2470

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Abstract

Neuroblastoma is the most common solid tumor in early childhood. Patients with neuroblastoma due to the amplification of a 130-kb genomic DNA region containing the MYCN, MYCN antisense NCYM and lncUSMycN genes show poor prognosis. BET bromodomain inhibitors show anticancer efficacy against neuroblastoma partly by reducing MYCN gene transcription and N-Myc mRNA and protein expression. We have previously shown that the long nocoding RNA lncUSMycN upregulates N-Myc mRNA expression by binding to the RNA-binding protein NonO. In this study, we found that lncUSMycN upregulated NCYM expression, and knocking-down lncUSMycN reduced histone H3 lysine 4 trimethylation, a marker for active gene transcription, at the NCYM gene promoter. NCYM upregulated N-Myc mRNA expression, NCYM RNA formed a complex with NonO protein, and knocking down NCYM expression reduced neuroblastoma cell proliferation. Importantly, treatment with BET bromodomain inhibitors reduced NCYM expression. In human neuroblastoma patients, high levels of NCYM expression in tumor tissues correlated with high levels of N-Myc, NonO and lncUSMycN expression as well as poor patient prognosis. Taken together, our findings suggest that lncUSMycN upregulates NCYM expression by activating its gene transcription, and that NCYM RNA upregulates N-Myc mRNA expression by binding to NonO. Our findings also provide further evidence for the application of BET bromodomain inhibitors for the therapy of neuroblastoma characterized by MYCN/NCYM gene locus amplification.

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