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| Status |
Public on Apr 03, 2025 |
| Title |
Stress attenuation by the adrenergic-specific lncRNA NESPR prevents cell death in neuroblastoma cells [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Neuroblastoma is a pediatric cancer of the sympathetic nervous system characterized by heterogeneous cell states that mirror normal differentiation trajectories. Each state is governed by a core regulatory transcriptional circuitry that reinforces cell identity through an autoregulatory feedforward loop. We identified the long non-coding RNA NESPR as specifically expressed in adrenergic neuroblastoma cells. NESPR expression correlates with high-risk neuroblastoma clinical parameters and poor patient survival. NESPR is located within an insulated gene neighborhood alongside PHOX2B, a master transcription factor of the adrenergic identity. NESPR depletion reduced cell proliferation and increased caspase activity in neuroblastoma cell lines, and NESPR knockout in a neuroblastoma zebrafish model led to reduced tumor penetrance. Subcellular localization revealed NESPR to be a cytosolic long non-coding RNA, suggesting a trans-regulatory function. RNA-sequencing following NESPR depletion revealed a shift from an adrenergic to a mesenchymal cell state, due to proteotoxic stress-induced molecular reprogramming. These findings suggest NESPR as a regulator of neuroblastoma cell identity with potential therapeutic opportunities in high-risk neuroblastoma cases.
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| Overall design |
ATAC-seq of SK-N-BE(2)c with and without ASO treatment (2 NESPR-targeting ASOs, 1 negative control ASO).
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| Contributor(s) |
Delhaye L, Mestdagh P, Roels J, Van Vlierberghe P |
| Citation missing |
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| Submission date |
Apr 03, 2025 |
| Last update date |
Apr 03, 2025 |
| Contact name |
Louis Delhaye |
| E-mail(s) |
louis.delhaye@ugent.be
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| Organization name |
Ghent University
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| Street address |
Corneel Heymanslaan 10
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| City |
Gent |
| ZIP/Postal code |
9000 |
| Country |
Belgium |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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