Omics · study · 2026
TERT drives liver tumorigenesis and immune reprogramming independently of telomere elongation
Listed in NCBI GEO
We generated two mouse models, p21⁺/Tert and p21⁺/TertCi, that express either telomerase reverse transcriptase (TERT) or its catalytically inactive form under the control of the p21 promoter, establishing a feedback loop that restricts telomerase expression to p21-positive cells.
Description
By 18–20 months of age, approximately 15% of mice from both genotypes developed liver tumors with histopathological features resembling human hepatocellular carcinoma (HCC).
Whole-exome sequencing revealed activating mutations in Ctnnb1 in p21⁺/Tert tumors, and activating HrasGln61Lys mutations in p21⁺/TertCi tumors, associated with elevated C>A transversions as well as recurrent PP1 subunit mutations in multiple tumors. Despite distinct point mutations, both models exhibited chromosomal alterations recurrent in human HCC. β-catenin–activated tumors displayed gene expression signatures characteristic of human HCC, as well as SLC1A5 overexpression, whereas MAPK-mutated tumors showed transcriptional profiles consistent with MAPK/ERK pathway activation.
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Both genotypes demonstrated upregulation of glycolytic enzymes and downregulation of gluconeogenic enzymes such as FBP1, but overexpressed distinct NRF2 targets. Spatial architecture of the tumors using the Hyperion™ Imaging System revealed reduced HNF4A-positive hepatocytes in all tumors, independent of Hnf4a transcriptional changes, and markedly decreased immune cell infiltration in β-catenin–activated tumors. Together, these results uncover unanticipated roles for TERT beyond telomere elongation and identify molecular and metabolic biomarkers predictive of immunotherapy response in HCC.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE317nnn/GSE317255 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE317255 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1406632 ncbi.nlm.nih.gov/bioproject/PRJNA1406632 ↗
project · from NCBI GEO
- PubMed 42392980 pubmed.ncbi.nlm.nih.gov/42392980 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Imaging 75% · Sequencing 75%
Provenance · 1 source records, 9 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE317255 | 11 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:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:imaging | 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[organism].NCBITaxon:10090 | 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 |