Omics · study · 2026
USP10-mediated PFKFB4 deubiquitination induces lung cancer radioresistance by activating the fumarate/Rad51 axis
Listed in NCBI GEO
Radioresistance is a major cause of radiotherapy failure in lung cancer, and its mechanism has not been fully elucidated.
Description
Glucose metabolism is closely related to radioresistance, and targeting key molecules in glucose metabolism is expected to increase radiosensitivity. Our study demonstrated that the expression of the gluconeogenic enzyme PFKFB4 was upregulated in lung cancer.
Genetic silencing and pharmacological inhibition of PFKFB4 significantly enhanced lung cancer radiosensitivity. Mechanistically, the fumaric acid/Rad51 axis is crucial for PFKFB4-induced radioresistance. PFKFB4 inhibits histone demethylase KDM1A by upregulating fumaric acid, which in turn increases the level of H3K4me1 at the Rad51 promoter region and induces Rad51 transcriptional activation, and ultimately leads to lung cancer radioresistance.
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Furthermore, by constructing a library of ubiquitinated compounds, the deubiquitinating enzyme USP10 was identified as a key upstream molecule for stabilizing PFKFB4 expression, and USP10 silencing downregulated fumaric acid and Rad51 in a PFKFB4-dependent manner, which in turn increased lung cancer radiosensitivity. In conclusion, the present study reveals that USP10-mediated PFKFB4deubiquitination promotes lung cancer radioresistance through activation of the fumaric acid/Rad51 axis and provides important evidence for the clinical translation of PFKFB4.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE249nnn/GSE249850 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE249850 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1051015 ncbi.nlm.nih.gov/bioproject/PRJNA1051015 ↗
project · from NCBI GEO
- PubMed 42417500 pubmed.ncbi.nlm.nih.gov/42417500 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE249850 | 11 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: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 |