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Series GSE240505 Query DataSets for GSE240505
Status Public on Mar 04, 2024
Title Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Neuroblastoma with MYCN amplification (MNA) is a high-risk disease that requires long-term intensive multimodal therapies. Less than 50% survival rate of high-risk patients has prompted active and extensive studies to seek more effective therapies against MNA neuroblastomas but with few successes. We show that MYCN transdifferentiates the neuroblastoma cells from mesenchymal state to adrenergic state accompanied with induction of histone lysine demethylase 4 family members (KDM4A-C), all of which act in concert to control the expression of MYCN and adrenergic core regulatory transcription factors (CRC TF). Pharmacologic inhibition of KDM4 blocks expression of MYCN and adrenergic CRC transcriptome with genome-wide induction of transcriptionally repressive H3K9me3, resulting in potent anticancer activity against MNA neuroblastomas by inducing differentiation, apoptosis and type I interferon response. KDM4 inhibition in combination with chemotherapy leads to complete tumor response of MNA xenografts, without overt toxicity in animals. Thus, KDM4 blockade may be a transformative strategy to target the dependency of adrenergic CRC TFs in MNA neuroblastomas.
 
Overall design In order to verify MYCN alters the mesenchymal state of neuroblastoma cells to a more adrenergic state, we generated MYCN inducible GIMEN cell line. Then, we performed gene profiling analysis with RNA-seq data. For exploring the KDM4 protein role in the neuroblastoma cells, we treated GIMEN, SH_SY5Y with QC6352, also generated QC6352-resistant BE2C cells. We investigated the tumor samples from TH-MYCN/ALKF1178L mouse model with and without QC6352 treatment. We compare gene profiles changes with or without QC6352 treatment or QC6352 resistant.
 
Contributor(s) Ahmed A, Shivendra S, Jie F, Hongjian J, Jun Y
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Submission date Aug 09, 2023
Last update date Mar 05, 2024
Contact name Hongjian Jin
E-mail(s) hongjian.jin@STJUDE.ORG
Organization name St Jude Children's Research Hospital
Department Center for Applied Bioinformatics
Street address 262 Danny Thomas Place
City Memphis
State/province TN
ZIP/Postal code 38015
Country USA
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (22)
GSM7699152 BE2C_Ctrl_1
GSM7699153 BE2C_Ctrl_2
GSM7699154 BE2C-QC6352R_1
This SubSeries is part of SuperSeries:
GSE240506 Histone lysine demethylase 4 family proteins maintain the transcriptional program and adrenergic cellular state of MYCN-amplified neuroblastoma
Relations
BioProject PRJNA1003939

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE240505_RAW.tar 33.8 Mb (http)(custom) TAR (of RESULTS)
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Raw data are available in SRA

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