Excel · study · 2026
OSTM1 is a tumor suppressor that restrains B-cell lymphomagenesis by promoting PDE3B degradation and activating cAMP-PKA-CREB signaling [RNA-seq]
Listed in NCBI GEO
Through a genome-wide forward CRISPR/Cas9 screen in interleukin-3 (IL3)-dependent Ba/F3 cells, we identified osteoclastogenesis-associated transmembrane protein 1 (OSTM1) as a previously unrecognized tumor suppressor.
Description
Analysis of patient datasets revealed that OSTM1 is frequently deleted or downregulated in human B-cell lymphomas (BCL). In mice, Cd19-Cre-driven B cell–specific monoallelic or biallelic deletion of Ostm1 cooperated with Cdkn2a loss to drive lymphomagenesis with near-complete penetrance.
Mechanistically, OSTM1 directly interacts with phosphodiesterase 3B (PDE3B) and promotes its proteasomal degradation. Because PDE3B hydrolyzes cyclic AMP (cAMP), loss of OSTM1 stabilizes PDE3B, leading to suppression of tumor-suppressive cAMP-dependent PKA/CREB signaling and promotion of oncogenic transformation. Consistent with this mechanism, PDE3B is frequently amplified or upregulated in BCL, and expression of CREB/CREBBP transcriptional targets correlates positively with OSTM1 expression but inversely with PDE3B across BCL cohorts.
Read the rest (1 more)
Importantly, silencing Pde3b reverses oncogenic transformation driven by Ostm1 loss. Together, these findings establish OSTM1 as a previously unrecognized tumor suppressor and uncover an OSTM1-PDE3B-cAMP signaling axis that restrains B-cell lymphomagenesis and may represent a therapeutically actionable vulnerability.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE341nnn/GSE341453 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE341453 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1502783 ncbi.nlm.nih.gov/bioproject/PRJNA1502783 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · RNA sequencing 65%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE341453 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |