Omics · study · 2026
GABRA6 receptor knockout promotes the progression of bladder cancer of mice by increasing the amount of M2 type macrophages in tumor microenvironment
Listed in NCBI GEO
Gamma-aminobutyric acid (GABA), a principal inhibitory neurotransmitter, plays a crucial role in regulating neuronal activity.
Description
Emerging evidence reveals its extraneural distribution in various peripheral tissues, including immune cells and tumor tissues, implicating GABA in oncogenesis and cancer immunity. However, the role of GABA in tumor biology remains controversial, with reports of both tumor-promoting and tumor-suppressive effects depending on receptor subunit specificity.
In this study, we investigated the function of the GABA_A receptor alpha6 subunit (GABRA6) in bladder cancer using a genetic knockout mouse model. CD8+ T cells isolated from GABRA6-deficient mice exhibited enhanced cytotoxicity against bladder tumor cells in vitro, demonstrated by increased tumor cell apoptosis and elevated secretion of pro-inflammatory cytokines. Paradoxically, in vivo bladder tumor models showed accelerated tumor progression in GABRA6-/- mice.
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Transcriptomic profiling of tumor tissues identified upregulation of CD5L, a key regulator of M2 macrophage polarization, in GABRA6-deficient bladder tumors. Mechanistic studies revealed that CD5L-driven M2 macrophage expansion suppressed CD8+ T cell function, thereby facilitating tumor progression. Macrophage depletion experiments validated this immunosuppressive axis.
Collectively, these findings uncover a novel mechanism by which GABRA6 deficiency promotes bladder cancer progression through CD5L-dependent M2 macrophage polarization and CD8+ T cell dysfunction.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE347nnn/GSE347180 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE347180 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1527639 ncbi.nlm.nih.gov/bioproject/PRJNA1527639 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE347180 | 14 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 (75%) |
| 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[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 |