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| Status |
Public on Jul 30, 2023 |
| Title |
AVEN is an indirectly druggable mediator of neuroblastoma cell tumorigenicity and chemotherapy resistance [microarray] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Approximately half of children diagnosed with neuroblastoma have aggressive high-risk disease, against which current multimodal therapy has little success. New targets for therapeutic intervention are urgently needed. In a systems approach, we combined time-resolved mRNA-Seq with miRNA profiling in a model of neuroblastoma differentiation treated with or without the clinically approved histone deacetylase inhibitor, panobinostat. Treatment most strongly regulated miR-630, which strongly downregulated AVEN, an inhibitor of apoptosis. Here we characterized AVEN for the first time in neuroblastoma pathogenesis, disclosed its epigenetic regulation and discovered correlations between AVEN expression and resistance to chemotherapy. High-level AVEN expression in 649 primary neuroblastomas negatively correlated with patient survival. Stably enforcing AVEN expression in BE(2)-C cells markedly promoted growth as subcutaneous xenografts in mice, while CRISP/Cas9-mediated AVEN knockout in BE(2)-C cells substantially reduced xenograft growth and enhances the efficacy of systemic doxorubicin treatment. Cell-based assays, flow cytometric cell cycle analyses and SILAC experiments demonstrate that AVEN is required for neuroblastoma proliferation.
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| Overall design |
Panobinostat induced miRNA gene expression in human neuroblastoma BE(2)-C cells, treated with 5 nM, 10 nM or 15 nM for 24 h. Two independent experiments were performed
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| Contributor(s) |
Pfeil S, Sahly II, Winkler A, Sprüssel A, Wuenschel J, Tiburtius D, Ziehm M, Bartenhagen C, Hundsdörfer P, Selbach M, Eggert A, Lodrini M, Deubzer HE |
| Citation missing |
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| |
| Submission date |
Apr 30, 2019 |
| Last update date |
Jul 31, 2023 |
| Contact name |
Hedwig Elisabeth Deubzer |
| E-mail(s) |
[email protected]
|
| Organization name |
Charite - University Hospital Berlin
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| Department |
Department of Pediatrics, Division of Oncology and Hematology
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| Lab |
Deubzer
|
| Street address |
Augustenburger Platz 1
|
| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
13353 |
| Country |
Germany |
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| Platforms (1) |
| GPL21576 |
Agilent-070156 Human_miRNA_V21.0_Microarray 046064 (Probe Name version) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE130524 |
AVEN is an indirectly druggable mediator of neuroblastoma cell tumorigenicity and chemotherapy resistance |
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| Relations |
| BioProject |
PRJNA540518 |
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