ArticleMolecular neurobiology2022
TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.
Article in Molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 29 citations in OpenAlex.
- Analysis of gene expression changes upon topobexin treatment and TOP2B-knockout in hiPSC-derived cardiomyocytes.Biology open · 2026Article
- In-vitro modelling of Alzheimer's disease using cholinergic neurons derived from human neuroblastoma (SH-SY5Y) retinoic acid-induced differentiation.Molecular biology reports · 2026Article
- Alternative Splicing of the NF-Y Subunit, NF-YA, in Neuroblastoma Phenotype Heterogeneity.Cancers · 2026Review
- DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression.bioRxiv : the preprint server for biology · 2026Article
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- Valproate Releases the Latent Differentiation Capacity of Neuroblastoma by Targeting SP1/CDK4 Signaling.Neurochemical research · 2026Article
- From mice to clinical relevance: humanizing neuroscience with human-based model systems.Frontiers in cellular neuroscience · 2026Review
- Transcriptional Consequences of MeCP2 Knockdown and Overexpression in Mouse Primary Cortical Neurons.International journal of molecular sciences · 2025Article
- Nonredundant roles of topoisomerase 2α and 2β in the cytosolic replication of vaccinia virus.Nucleic acids research · 2025Article
- Topobexin targets the Topoisomerase II ATPase domain for beta isoform-selective inhibition and anthracycline cardioprotection.Nature communications · 2025Article
- Emerging Trends in Neuroblastoma Diagnosis, Therapeutics, and Research.Molecular neurobiology · 2025Review
- Probing enzyme-dependent pseudouridylation using direct RNA sequencing to assess epitranscriptome plasticity in a neuronal cell line.Cell systems · 2025Article
- TOP2B is required for compartment strength changes upon retinoic acid treatment in SH-SY5Y cells.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2025Article
- Schizophrenia risk gene ZNF536 modulates retinoic acid response and neuronal gene networks in SH-SY5Y cells.Frontiers in molecular neuroscience · 2025Article
- Melittin promotes the proliferation of Schwann cells in hyperglycemic environment by up‑regulating the Crabp2/Wnt/β‑catenin signaling pathway.Molecular medicine reports · 2025Article
- Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma.Cancer biology & therapy · 2024Article
- Probing enzyme-dependent pseudouridylation using direct RNA sequencing to assess neuronal epitranscriptome plasticity.bioRxiv : the preprint server for biology · 2024Article
- Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Loss of Adaptive DNA Breaks in Alzheimer's Disease Brains.Journal of Alzheimer's disease : JAD · 2024Article
- Loss of Adaptive DNA Breaks in Alzheimer's Disease Brains.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes. We found that expression of many, but not all genes that are rapidly induced by ATRA in SH-SY5Y cells was significantly reduced in the TOP2B null cells; these genes include BCL2, CYP26A1, CRABP2, and NTRK2. Comparing gene expression profiles in wild-type versus TOP2B null cells, we found that long genes and genes expressed at a high level in WT SH-SY5Y cells were disproportionately dependent on TOP2B. Notably, TOP2B null SH-SY5Y cells upregulated mesenchymal markers vimentin (VIM) and fibronectin (FN1) and components of the NOTCH signalling pathway. Enrichment analysis and comparison with the transcription profiles of other neuroblastoma-derived cell lines supported the conclusion that TOP2B is required to fully maintain the adrenergic neural-like transcriptional signature of SH-SY5Y cells and to suppress the alternative mesenchymal epithelial-like epigenetic state.
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