Data · study · 2026
Synthetic lethal therapy reveals precision therapeutic strategy for MSH2-mutated bladder cancer
Listed in NCBI GEO
hMSH2 (human mutS homolog 2) is the most frequently mutated gene in the DNA mismatch repair (MMR) system in bladder cancer (BCa).
Description
The majority of hMSH2 mutations result in a reduction of expression and a consequent promote cisplatin (CDDP) chemoresistance. However, precision therapeutic strategy based on hMSH2 mutations is not available clinically.
Herein, we reported that knockout of hMSH2 mediated by CRISPR/cas9 technology reduced the sensitivity of BCa to CDDP. Importantly, GK921, a TGM2-specific inhibitor, increased tumor cell killing by CDDP in hMSH2-deficient BCa in a synthetic lethal manner. GK921 also promoted the chemosensitivity of Msh2-knockout mice to CDDP.
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Hi-C analysis indicated that hMSH2 deficiency rewired chromatin accessibility of the TGM2 promoter region, which recruits more transcription factors. The enrichment levels of transcription factor AP-1 in TGM2 promoter region were increased in hMSH2-knockout BCa cells, thereby promoting the expression of TGM2 transcriptionally. This study shows that CDDP effectiveness depends on TGM2 levels in hMSH2-mutated BCa and that combining CDDP with TGM2 inhibition may provide a promising personalized therapeutic strategy for hMSH2-mutated BCa patients.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE262nnn/GSE262994 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE262994 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1095419 ncbi.nlm.nih.gov/bioproject/PRJNA1095419 ↗
project · from NCBI GEO
Topics
- Stated by source
- Homo sapiens · Other
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE262994 | 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 (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:other | 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 |