Omics · study · 2026
Transcriptome analysis of KRT15 knockdown in lenvatinib-resistant papillary thyroid carcinoma cells
Listed in NCBI GEO
Lenvatinib resistance is a major clinical obstacle in the treatment of radioiodine-refractory papillary thyroid cancer (PTC), and clarifying its molecular mechanisms is crucial for developing effective therapeutic strategies.
Description
In this study, we identify Keratin 15 (KRT15) as a key driver of this resistance. We found that KRT15 overexpression is associated with an unfavorable clinical prognosis in PTC patients.
Mechanistically, KRT15 interacts with Keratin 81 (KRT81) to form a regulatory complex that upregulates Diacylglycerol Kinase B (DGKB). This KRT15-KRT81-DGKB axis drives metabolic reprogramming by increasing the expression of key fatty acid oxidation (FAO) enzymes, such as CPT1A and ACOX1, which enhances cellular energetics and promotes survival under therapeutic stress. Consequently, inhibition of this pathway successfully resensitizes resistant cells to lenvatinib.
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Taken together, our study reveals a novel mechanism where cytoskeletal proteins mediate metabolic adaptation in drug-resistant PTC cells, identifying the KRT15-KRT81-DGKB pathway as a promising therapeutic target to overcome lenvatinib resistance in refractory PTC patients.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE299nnn/GSE299763 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE299763 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1276462 ncbi.nlm.nih.gov/bioproject/PRJNA1276462 ↗
project · from NCBI GEO
- PubMed 41991644 pubmed.ncbi.nlm.nih.gov/41991644 ↗
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 | GSE299763 | 12 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 |