Regulation of MYCN Expression in Human Neuroblastoma Cells

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2009 Jul 21

PMID 19615087

Citations 19

Authors

Joannes F M Jacobs

Hans van Bokhoven

Frank N van Leeuwen

Christina A Hulsbergen-van de Kaa

I Jolanda M de Vries

Gosse J Adema

Peter M Hoogerbrugge

Arjan P M de Brouwer

Affiliations

Soon will be listed here.

Abstract

Background: Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (DeltaMYCN) that was recently identified in fetal tissues. Both MYCNOS and DeltaMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level.

Methods: Expression of MYCN, MYCNOS and DeltaMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR).

Results: Both DeltaMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:DeltaMYCN expression was identical in all tested NBs. This indicates that DeltaMYCN and MYCN are co-regulated, which suggests that DeltaMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level.

Conclusion: The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by DeltaMYCN.

Citing Articles

Super-enhancer MYCNOS-SE promotes chemoresistance in small cell lung cancer by recruiting transcription factors CTCF and KLF15.

Niu Y, Tang Y, Ma F, Zhou X, Chen Y, Wang Y Oncogene. 2024; 44(4):255-268.

PMID: 39511411 PMC: 11746145. DOI: 10.1038/s41388-024-03202-1.

CD47-Dependent Regulation of Immune Checkpoint Gene Expression and MYCN mRNA Splicing in Murine CD8 and Jurkat T Cells.

Kaur S, Awad D, Finney R, Meyer T, Singh S, Cam M Int J Mol Sci. 2023; 24(3).

PMID: 36768931 PMC: 9916813. DOI: 10.3390/ijms24032612.

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Bartolucci D, Montemurro L, Raieli S, Lampis S, Pession A, Hrelia P Cancers (Basel). 2022; 14(18).

PMID: 36139583 PMC: 9496712. DOI: 10.3390/cancers14184421.

Establishment and Validation of a Ferroptosis-Related lncRNA Signature for Prognosis Prediction in Lower-Grade Glioma.

Huang Q, Li J, Yan P, Jiang Q, Guo F, Zhao Y Front Neurol. 2022; 13:861438.

PMID: 35832170 PMC: 9271629. DOI: 10.3389/fneur.2022.861438.

MYCN in Neuroblastoma: "Old Wine into New Wineskins".

Braoudaki M, Hatziagapiou K, Zaravinos A, Lambrou G Diseases. 2021; 9(4).

PMID: 34842635 PMC: 8628738. DOI: 10.3390/diseases9040078.

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