Background: Neuroblastoma (NB) is the most common extracranial malignancy in childhood; however, the mechanisms underlying its aggressive characteristics still remain elusive.

Methods: Integrative data analysis was performed to reveal tumour-driving transcriptional regulators. Co-immunoprecipitation and mass spectrometry assays were applied for protein interaction studies. Real-time reverse transcription-polymerase chain reaction, western blotting, sequential chromatin immunoprecipitation and dual-luciferase reporter assays were carried out to explore gene expression regulation. The biological characteristics of NB cell lines were examined via gain- and loss-of-function assays. For survival analysis, the Cox regression model and log-rank tests were used.

Results: Cellular nucleic acid-binding protein (CNBP) was found to be an independent factor affecting NB outcome, which exerted oncogenic roles in ribosome biogenesis, tumourigenesis and aggressiveness. Mechanistically, karyopherin subunit beta 1 (KPNB1) was responsible for nuclear transport of CNBP, whereas liquid condensates of CNBP repressed the activity of switch/sucrose-nonfermentable (SWI/SNF) core subunits (SMARCC2/SMARCC1/SMARCA4) via interaction with SMARCC2, leading to alternatively increased activity of SMARCC1/SMARCA4 binary complex in facilitating gene expression essential for 18S ribosomal RNA (rRNA) processing in tumour cells, extracellular vesicle-mediated delivery of 18S rRNA and subsequent M2 macrophage polarisation. A cell-penetrating peptide blocking phase separation and interaction of CNBP with SMARCC2 inhibited ribosome biogenesis and NB progression. High KPNB1, CNBP, SMARCC1 or SMARCA4 expression or low SMARCC2 levels were associated with poor survival of NB patients.

Conclusions: These findings suggest that CNBP phase separation is a target for inhibiting ribosome biogenesis and tumour progression in NB via modulating SWI/SNF complex activity.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131295PMC
http://dx.doi.org/10.1002/ctm2.1235DOI Listing

Publication Analysis

Top Keywords

ribosome biogenesis
16
phase separation
12
cnbp phase
8
progression modulating
8
modulating swi/snf
8
swi/snf complex
8
complex activity
8
gene expression
8
cnbp
7
therapeutic targeting
4

Similar Publications

Comprehensive Analysis of Immune Characteristics of Fluorosis and Cuprotosis-Related Genes in Fluorosis Targeted Drugs.

Biol Trace Elem Res

January 2025

Department of Environmental Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, P. R. China.

This study aims to investigate the role of cuprotosis in fluorosis and identify potential targeted drugs for its treatment. The GSE70719 and GSE195920 datasets were merged using the inSilicoMerging package. DEGs between the exposure and control groups were found using R software.

View Article and Find Full Text PDF

Hypothesis for Molecular Evolution in the Pre-Cellular Stage of the Origin of Life.

Wiley Interdiscip Rev RNA

January 2025

Institute for Ocean Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen, People's Republic of China.

Life was originated from inorganic world and had experienced a long period of evolution in about 3.8 billion years. The time for emergence of the pioneer creations on Earth is debatable nowadays, and how the scenario for the prebiotic molecular interactions is still mysterious.

View Article and Find Full Text PDF

Unlabelled: Human REXO4 is a poorly characterized exonuclease that is overexpressed in human cancers. To better understand the function of REXO4 and its relationship to cellular proliferation, we have undertaken multidisciplinary approaches to characterize its cell cycle phase-dependent subcellular localization and the cis determinants required for this localization, its importance to cell cycle progression and cell viability, its protein-protein association network, and its activity. We show that the localization of REXO4 to the nucleolus in interphase depends on an N-terminal nucleolar localization sequence and that its localization to the perichromosomal layer of mitotic chromosomes is dependent on Ki67.

View Article and Find Full Text PDF

Objective: Mitochondrial genome sequences are very useful for understanding the mitogenome evolution itself and reconstructing phylogeny of different plant lineages. Bauhinia purpurea, a species from the legume family Leguminosae, is widely distributed in South China and has high ornamental value. Here, we sequenced and assembled the mitogenome of B.

View Article and Find Full Text PDF

Objectives: To explore the role of berberine (BBR) in ameliorating coronary endothelial cell injury in Kawasaki disease (KD) by regulating the complement and coagulation cascade.

Methods: Human coronary artery endothelial cells (HCAEC) were divided into a healthy control group, a KD group, and a BBR treatment group (=3 for each group). The healthy control group and KD group were supplemented with 15% serum from healthy children and KD patients, respectively, while the BBR treatment group received 15% serum from KD patients followed by the addition of 20 mmol/L BBR.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!