Data · study · 2026
Ferroptosis Suppression by the m6A Reader IGF2BP1 Underlies Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma [RIP-Seq]
Listed in NCBI GEO
Aims: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with poor prognosis, and gemcitabine-based chemotherapy remains the standard first-line treatment.
Description
However, the rapid emergence of chemoresistance limits its efficacy. Elucidating the molecular mechanisms underlying gemcitabine resistance is critical for improving therapeutic outcomes.
Approaches & Results: By integrating transcriptomic profiling of gemcitabine-resistant PDAC cells, patient-derived xenografts (PDXs), and pretreatment clinical biopsy specimens, we identified the m6A reader IGF2BP1 as a key determinant of both intrinsic and acquired gemcitabine resistance. Mechanistically, IGF2BP1 directly binds m6A-modified FTH1 mRNA and cooperates with G3BP1-mediated stress granule sequestration to enhance FTH1 transcript stability under chemotherapeutic stress.
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The stabilized FTH1 maintains intracellular iron homeostasis, limits lipid peroxidation, and suppresses ferroptosis, thereby conferring chemoresistance. Pharmacological inhibition of IGF2BP1 with BTYNB partially disrupted this regulatory axis, restored ferroptotic susceptibility, and synergistically enhanced gemcitabine efficacy in resistant PDX models without overt toxicity. Conclusions: Collectively, this study uncovers a previously unrecognized epitranscriptomic mechanism linking m6A-dependent RNA stabilization, stress granule dynamics, and ferroptosis suppression in PDAC.
By identifying IGF2BP1 as a potential biomarker of gemcitabine response and a therapeutically actionable target, these findings provide a preclinical rationale for IGF2BP1-targeted combination strategies to overcome gemcitabine resistance in PDAC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337103 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337103 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1484054 ncbi.nlm.nih.gov/bioproject/PRJNA1484054 ↗
project · from NCBI GEO
- PubMed 42573560 pubmed.ncbi.nlm.nih.gov/42573560 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Homo sapiens · Other
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE337103 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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 |