Dataset Information

NDUFS6 promotes neuroblastoma progression and represents a potential therapeutic target

ABSTRACT: Active oxidative phosphorylation is increasingly recognized as a defining metabolic feature of high-risk neuroblastoma (NB). NDUFS6, an essential subunit of mitochondrial respiratory chain complex I, plays a critical role in sustaining oxidative phosphorylation. Nevertheless, its precise contribution to NB pathogenesis and progression remains largely undefined. We found NDUFS6 expression was significantly upregulated in high-risk NB and was positively associated with disease progression and poor prognosis. Functional assays revealed that NDUFS6 knockdown suppressed proliferation, invasion, and migration of NB cells, whereas its overexpression promoted these malignant behaviors. Transcriptomic analysis revealed that high NDUFS6 expression activated pathways related to energy metabolism and ATP synthesis, while concurrently suppressing neuronal differentiation and immune activation. Structure-based virtual screening identified several candidate inhibitors of NDUFS6, including guanosine 5′-triphosphate, 1,4-β-D-xylopentaose, and deferoxamine. Subsequent drug sensitivity assays demonstrated that guanosine 5′-triphosphate exerted potent inhibitory effects in both MYCN-amplified and non-amplified NB cell lines. These findings underscore the oncogenic role of NDUFS6 and highlight its potential as a therapeutic target for precision treatment in high-risk NB.

ORGANISM(S): Homo sapiens

PROVIDER: GSE308228 | GEO | 2026/06/18

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

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.

Dataset Information

NDUFS6 promotes neuroblastoma progression and represents a potential therapeutic target

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets