Omics · study · 2026
Super-enhancer-driven MAFK promotes glioblastoma growth by transcriptionally activating immune-related genes and is stabilized by the deubiquitinase USP36
Listed in NCBI GEO
Glioblastoma (GBM) is the most aggressive primary malignant tumor of the adult central nervous system, with a median survival of less than 15 months despite surgery combined with radiochemotherapy.
Description
Super-enhancers (SEs) are large clusters of cis-regulatory elements densely marked by H3K27ac that drive high-level expression of key oncogenes. In this study, we systematically identified SE-regulated genes in GBM by integrating H3K27ac ChIP-seq data from five glioma cell lines and applying the ROSE algorithm.
We report for the first time that MAFK, a small Maf family transcription factor, is controlled by an SE in GBM. Three-dimensional genome profiling revealed prominent long-range chromatin interactions between the MAFK-SE and the MAFK locus, and E2 was delineated as the principal active enhancer element. Functionally, MAFK depletion markedly impaired GBM cell proliferation, induced G2/M arrest and apoptosis in vitro, and suppressed subcutaneous xenograft growth in vivo.
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Integrative RNA-seq and CUT&Tag analyses showed that MAFK directly binds and transcriptionally activates immune-related genes, including IL6, IRF1, STAT1, NFKB1 and JAK2, implicating it in the regulation of GBM cell immune responses. Moreover, co-immunoprecipitation coupled with mass spectrometry identified the deubiquitinase USP36 as a novel MAFK-interacting protein. USP36 selectively removed K48-linked polyubiquitin chains from MAFK, thereby protecting it from proteasomal degradation and sustaining its steady-state level.
Collectively, these data uncover a SE–MAFK–USP36 regulatory axis that drives GBM progression and nominate MAFK as a potential therapeutic target.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE348nnn/GSE348366 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE348366 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1533557 ncbi.nlm.nih.gov/bioproject/PRJNA1533557 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65% · Mass spectrometry 75% · RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE348366 | 10 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:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:mass-spectrometry | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |