Dataset Information

Proteomic analysis reveals chromatin remodeling and RNA processing as potential therapeutical targets in Neuroblastoma

ABSTRACT: Neuroblastoma (NB) is the most common solid tumor in children, characterized by high recurrence rates, drug resistance, and significant mortality. In this study, we analyzed the proteomic profiles of NB tissue samples alongside other pathological categories, including ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Our findings reveal that pathways associated with the cell cycle and DNA replication are significantly upregulated in NB, while oxidative phosphorylation, pyruvate metabolism, and the TCA cycle are notably downregulated compared to GNB and GN. Using weighted gene co-expression network analysis (WGCNA), we identified a core prognostic gene model strongly associated with the unfavorable phenotype of NB, primarily related to RNA processing and chromatin remodeling. Notably, ALYREF and SMARCA4 emerged as potential prognostic biomarkers for NB. Furthermore, by mapping our core prognostic gene models onto drug-perturbed transcriptome profiles from the L1000FWD and CMap databases, we identified five promising repurposing drugs for NB. Among these, Mocetinostat and Clofarabine were validated as effective treatments in two NB cell lines, offering valuable insights for the development of novel targeted therapies in neuroblastoma.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Tissues

SUBMITTER: Zan Liu

LAB HEAD: Zan Liu

PROVIDER: PXD057521 | Pride | 2025-05-07

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Z9455DA_AG1_Slot1-24_1_6832.d.zip	Other
	Z9455DA_AG4_Slot1-25_1_6834.d.zip	Other
	Z9455DA_AG5_Slot1-26_1_6836.d.zip	Other
	Z9455DA_AG6_Slot1-27_1_6838.d.zip	Other
	Z9455DA_AG8_Slot1-30_1_6840.d.zip	Other

Items per page:

1 - 5 of 26

Publications

Proteomic analysis reveals chromatin remodeling as a potential therapeutical target in neuroblastoma.

Liu Zan Z Zhao Zitong Z Xie Longlong L Xiao Zhenghui Z Li Ming M Li Yong Y Luo Ting T

Journal of translational medicine 20250226 1

<h4>Background</h4>Neuroblastoma (NB) is the most common solid tumor in children, characterized by high recurrence rates, drug resistance, and significant mortality.<h4>Methods</h4>In this study, we analyzed the proteomic profiles of NB tissue samples alongside other pathological categories, including ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Using weighted gene co-expression network analysis (WGCNA), the core prognostic gene models associated with histopathology of NB were identified. ...[more]

PMID: 40011918

Similar Datasets

Project description:Neuroblastoma (NB) is an embryonal tumor with various clinical presentations and behaviors. Several genomic alterations has been well-studied in NB, among which genomic amplification of MYCN oncogene, is a strong prognostic biomarker with worsens outcome. Long noncoding RNAs (lncRNAs), constitute major proportion of the cellular transcripts with no coding capacity. One of their function is to guide transcription factors to the target genes and facilitate gene expression. However, relative contribution of lncRNA and MYCN to the advanced NB has remained unclear. Herein, by applying a network-based integrative analysis on MYCN amplified and MYCN nonamplified lncRNA expression profile from both RNA-seq and microarray platform, we identified lncRNA, SNHG1 to be differentially expressed and strongly correlated with MYCN in MYCN-amplified NB. The expression of SNHG1 was validated by RT-qPCR in NB cell lines. Survival analysis revealed that higher expression of SNHG1 significantly associates with poor patient survival. Moreover, knockdown of MYCN in MYCN-amplified NB cell lines inhibited SNHG1 expression. Furthermore, to unravel the role of SNHG1 in NB, we extracted SNHG1-interacting proteins by RNA-protein pull down assay coupled with doi:10.6342/NTU201701980 ! ! VI liquid chromatography-tandem mass spectrometry (LC-MS/MS). We identified 27 SNHG1-interacting proteins in common from three NB cell lines. However, only three SNHG1-interacting proteins, MATR3, YBX1 and HHRNPL have binding site detected by DeepBind motif analysis. Western blot confirms interaction of MATR3 with SNHG1. Additionally, we further validated the direct interaction between MATR3 and SNHG1 by RNA-immunoprecipation (IP). MATR3 is known to be involved in RNA transport and stabilization. Therefore, we proposed that MATR3 after interacting with SNHG1 might help in SNHG1 transcription and stabilization. In conclusion, our study unveils that SNHG1 could be a prognostic marker for high-risk NB and possibly stabilized by MATR3. Our results might provide future directions for the development of therapeutic strategies against high-risk NB.