Omics · study · 2026
RNA-seq profiling of radioiodine-treated differentiated thyroid cancer cells reveals DDR pathway regulation during iodine tolerance
Listed in NCBI GEO
Aim: To investigate the role of ataxia-telangiectasia mutated (ATM) in thyroid cancer (TC) progression and radioactive iodine (RAI) resistance, exploring its potential as a therapeutic target.
Description
Methods
Single-cell RNA sequencing of 28 TC tumors / normal tissues traced ATM dynamics during dedifferentiation. Clinical validation used tissue microarrays (TMAs) on 89 RAI resistance (RAIR) and RAI-avid differentiated thyroid cancer (DTC) specimens. Preclinical models evaluated the synergy between the ATM inhibitor AZD1390 and RAI.
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Mechanistic studies employed RNA-seq, comet assays, cell cycle analysis, and AP site quantification. Results: scRNA-seq revealed progressive ATM upregulation during malignant progression, correlating with cell cycle dysregulation. TMAs confirmed elevated ATM expression in anaplastic thyroid cancer (ATC) vs. papillary thyroid cancer, PTC and RAIR tumors.
In vivo, AZD1390 + 131I synergistically suppressed tumor growth and enhanced apoptosis. RAI predominantly induced apurinic/apyrimidinic (AP) sites rather than double-strand breaks (DSBs). ATM inhibition disrupted base excision repair (BER) coordination and G2/M checkpoint control, forcing cells with unresolved AP sites into mitotic catastrophe.
Conclusion: ATM mediates RAIR in thyroid cancer by promoting AP site repair and inducing cell cycle arrest. Inhibiting ATM converts repairable damage into lethal DNA lesions, restoring RAI sensitivity, suggesting ATM as a therapeutic target for RAI-refractory thyroid cancer.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297164 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297164 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1262923 ncbi.nlm.nih.gov/bioproject/PRJNA1262923 ↗
project · from NCBI GEO
- PubMed 42046098 pubmed.ncbi.nlm.nih.gov/42046098 ↗
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% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE297164 | 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:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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 |