Omics · study · 2026
L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes [NB1_NGP_KO]
Listed in NCBI GEO
Epigenetic alterations critically affect tumor development.
Description
Polycomb-group complexes constitute an evolutionarily conserved epigenetic machinery that regulates stem cell fate and development. They are implicated in tumorigenesis, primarily via histone modification.
Canonical and non-canonical Polycomb repressive complex 1 (PRC1.1–6) mediate the ubiquitination of histone H2A on lysine 119 (H2AK119ub). Here, we studied the functional roles of L3MBTL2, one of the PRC1.6 molecules, in neuroblastoma (NB) cells. shRNA- and CRISPR/Cas9-mediated L3MBTL2 depletion caused NB cell growth inhibition, cell-cycle arrest, and γ-H2A.X upregulation. Moreover, the knockout of L3MBTL2 profoundly suppressed xenograft tumor formation.
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Transcriptome analysis identified Break repair meiotic recombinase recruitment factor 1 (BRME1) and nuclear receptor interacting protein 3 (NRIP3) as targets of L3MBTL2-mediated silencing. The deletion of L3MBTL2 reduced enrichment of H2AK119ub and PCGF6 at transcriptional start site proximal regions of the targets. Add-back studies unveiled the importance of L3MBTL2-BRME1 and -NRIP3 axes for NB cell proliferation.
We further manifested the association of MYCN with de-repression of NRIP3 in an L3MBTL2-deficient context. Therefore, this study first revealed the significance of L3MBTL2-mediated gene silencing in MYCN-amplified NB cells.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE270nnn/GSE270991 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE270991 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1129170 ncbi.nlm.nih.gov/bioproject/PRJNA1129170 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE270991 | 15 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].anzsrc:group:3105 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (70%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | 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 |