Effects of a Novel Long Noncoding RNA, lncUSMycN, on N-Myc Expression and Neuroblastoma Progression

Liu, Pei Y.; Erriquez, Daniela; Marshall, Glenn M.; Polly, Patsie; Tee, Andrew E.; Liu, Bing; Bell, Jessica L.; Zhang, Xu Dong; Milazzo, Giorgio; Cheung, Belamy B.; Fox, Archa H.; Swarbrick, Alexander; Hüttelmaier, Stefan; Kavallaris, Maria; Perini, Giovanni; Mattick, John S.; Dinger, Marcel E.; Liu, Tao

doi:10.1093/jnci/dju113

Cited by 108 publications

(106 citation statements)

References 44 publications

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“…BE(2)-C and Kelly neuroblastoma cells were transfected with control siRNA or two independent siRNAs targeting different regions of lncUSMycN. The lncUSMycN siRNAs had been previously validated to knock down lncUSMycN RNA expression in BE(2)-C and Kelly cells (14). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…RNA immunoprecipitation assays were performed using Magna RIP kit from Merck Millipore according to the manufacturer's instructions (Merck Millipore, Billerica, MA, USA), with 5 µg of control IgG or antiNonO antibody for immunoprecipitation and primers targeting NCYM or the negative control U1 RNA for RT-PCR (14).…”

Section: Ncym Is Upregulated By Lncusmycn and Modulates N-myc Expressionmentioning

confidence: 99%

“…We have previously shown that the RNA-binding protein NonO upregulates N-Myc mRNA expression (14). Next we performed RNA immunoprecipitation assays with an anti-NonO antibody or control IgG, followed by RT-PCR analysis of NCYM RNA.…”

Section: Ncym Upregulates N-myc Expression and Induces Neuroblastoma mentioning

confidence: 99%

“…The long non-coding RNA NORAD is induced after DNA damage, and maintains genomic stability by sequestering PUMILIO proteins (13). We have recently shown that the long non-coding RNA lncUSMycN increases N-Myc mRNA expression by interacting with the RNA-binding protein NonO (14).…”

Section: Introductionmentioning

confidence: 99%

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NCYM is upregulated by lncUSMycN and modulates N-Myc expression

Liu

Atmadibrata

Mondal

et al. 2016

International Journal of Oncology

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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 knockingdown 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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Section: Resultsmentioning

confidence: 99%

Section: Ncym Is Upregulated By Lncusmycn and Modulates N-myc Expressionmentioning

confidence: 99%

Section: Ncym Upregulates N-myc Expression and Induces Neuroblastoma mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NCYM is upregulated by lncUSMycN and modulates N-Myc expression

Liu

Atmadibrata

Mondal

et al. 2016

International Journal of Oncology

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“…[25] High levels of a novel lncRNA, named as lncUSMycN, are independently associated with poor clinical outcome of neuroblastoma patients. [26] Importantly, the combination analysis of different lncUSMycN cutoff values and well-established factors is useful for individual risk assessment in different cohorts of neuroblastoma patients. [26] Therefore, lncRNAs are expected to have a significant impact on clinical oncology in the next decade, and might be potential novel targets for the treatment of neuroblastoma.…”

Section: Risk Stratifi Cation and Therapeutics Of Neuroblastoma: The mentioning

confidence: 99%

Risk stratification and therapeutics of neuroblastoma: the challenges remain

2016

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The RNA‐helicase DDX21 upregulates CEP55 expression and promotes neuroblastoma

et al. 2021

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Approximately 25% of human neuroblastoma is caused by amplification of the MYCN oncogene, which leads to overexpression of N‐Myc oncoprotein. The survival rate for this patient subtype is <50%. Here, we show that N‐Myc protein bound to the DEAD‐box RNA helicase DDX21 gene promoter and upregulated DDX21 mRNA and protein expression. Genome‐wide differential gene expression studies identified centrosomal protein CEP55 as one of the genes most dramatically downregulated after DDX21 knockdown in MYCN‐amplified neuroblastoma cells. Knocking down DDX21 or CEP55 reduced neuroblastoma cell cytoskeleton stability and cell proliferation and all but abolished clonogenic capacity. Importantly, DDX21 knockdown initially induced tumor regression in neuroblastoma‐bearing mice and suppressed tumor progression. In human neuroblastoma tissues, a high level of DDX21 expression correlated with a high level of N‐Myc expression and with CEP55 expression, and independently predicted poor patient prognosis. Taken together, our data show that DDX21 induces CEP55 expression, MYCN‐amplified neuroblastoma cell proliferation, and tumorigenesis, and that DDX21 and CEP55 are valid therapeutic targets for the treatment of MYCN‐amplified neuroblastoma.

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Effects of a Novel Long Noncoding RNA, lncUSMycN, on N-Myc Expression and Neuroblastoma Progression

Abstract: Our data demonstrate the important roles of lncUSMycN and NonO in regulating N-Myc expression and neuroblastoma oncogenesis and provide the first evidence that amplification of long noncoding RNA genes can contribute to tumorigenesis.

Cited by 108 publications

References 44 publications

NCYM is upregulated by lncUSMycN and modulates N-Myc expression

NCYM is upregulated by lncUSMycN and modulates N-Myc expression

Risk stratification and therapeutics of neuroblastoma: the challenges remain

The RNA‐helicase DDX21 upregulates CEP55 expression and promotes neuroblastoma

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