GEO series
UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through GATA2-ST6GALNAC5 and PRC2 interactions
GSE303043
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
30 samples
Submitted 2026/02/26
Platform GPL24676Platform GPL24247
Summary
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by early metastasis, immune evasion, and limited therapeutic progress. While its genomic landscape is well defined, the epigenetic programs sustaining its lineage fidelity, metastatic potential, and immune evasion remain incompletely understood. We used inducible CRISPR-Cas9 knockout models, transcriptomic and epigenetic profiling, immune-competent allografts, and genetically engineered mouse models (GEMMs) to investigate the role of the chromatin regulator UHRF1 in SCLC progression. We identify the chromatin remodeler UHRF1 as a subtype-independent oncogenic driver in SCLC, with high expression correlating with poor survival. UHRF1 loss impaired proliferation, invasion, and metastasis across ASCL1-, NEUROD1-, and POU2F3-driven subtypes. Mechanistically, UHRF1 maintained neuroendocrine lineage identity and suppressed immune gene expression via DNA methylation and interaction with PRC2. UHRF1-deficient tumors displayed increased infiltration of CD8⁺ T cells, monocytes, neutrophils, and dendritic cells, along with a higher CD8⁺/Treg ratio. Secretome profiling revealed upregulation of chemokines, linking UHRF1 loss to active recruitment of immune effector cells. In parallel, UHRF1 regulated the pro-metastatic sialyltransferase ST6GALNAC5 via the transcription factor GATA2. UHRF1 loss downregulated GATA2 and ST6GALNAC5, impairing tumor dissemination. Lastly, UHRF1 depletion increased expression of cancer/testis antigens such as MAGE-A4, without altering DLL3 levels, suggesting compatibility with both antigen-specific and DLL3-targeted immunotherapies. In conclusion, UHRF1 is a master regulator of tumor progression in SCLC, promoting lineage stability, immune evasion, and metastatic spread. Its inhibition reprograms tumors toward an inflamed, less metastatic, and more immunogenic state. These findings establish UHRF1 as a compelling therapeutic target for overcoming the epigenetic and immune resistance barriers in small cell lung cancer.
Published in
Gu Y, De La Torre JJ, Fazeli Y et al.
· iScience 2026
· PMID 42006373
· doi:10.1016/j.isci.2026.115475
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE303043_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1293407 and SRA study SRP601835. Searching any of these in the dataset finder brings you back here.
Study design
6 conditions, mostly with about 5 replicates each
NCI-H526 VC 5wk tumo ×5
NCI-H526 UHRF1 KO 5wk tumo ×5
NCI-H446 VC 5wk tumo ×5
NCI-H446 UHRF1 KO 5wk tumo ×5
TR DKO tumo ×5
TRU TKO tumo ×5
Supports a between-group comparison across 30 samples.
6 replicated groups read from 30 sample titles; they account for 30 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9116248 NCI-H526 VC 5wk tumor 1
- GSM9116249 NCI-H526 VC 5wk tumor 2
- GSM9116250 NCI-H526 VC 5wk tumor 3
- GSM9116251 NCI-H526 VC 5wk tumor 4
- GSM9116252 NCI-H526 VC 5wk tumor 5
- GSM9116253 NCI-H526 UHRF1 KO 5wk tumor 1
- GSM9116254 NCI-H526 UHRF1 KO 5wk tumor 2
- GSM9116255 NCI-H526 UHRF1 KO 5wk tumor 3
- GSM9116256 NCI-H526 UHRF1 KO 5wk tumor 4
- GSM9116257 NCI-H526 UHRF1 KO 5wk tumor 5
- GSM9116258 NCI-H446 VC 5wk tumor 1
- GSM9116259 NCI-H446 VC 5wk tumor 2
- GSM9116260 NCI-H446 VC 5wk tumor 3
- GSM9116261 NCI-H446 VC 5wk tumor 4
- GSM9116262 NCI-H446 VC 5wk tumor 5
- GSM9116263 NCI-H446 UHRF1 KO 5wk tumor 1
- GSM9116264 NCI-H446 UHRF1 KO 5wk tumor 2
- GSM9116265 NCI-H446 UHRF1 KO 5wk tumor 3
- GSM9116266 NCI-H446 UHRF1 KO 5wk tumor 4
- GSM9116267 NCI-H446 UHRF1 KO 5wk tumor 5
- GSM9116268 TR DKO tumor 1
- GSM9116269 TR DKO tumor 2
- GSM9116270 TR DKO tumor 3
- GSM9116271 TR DKO tumor 4
- GSM9116272 TR DKO tumor 5
- GSM9116273 TRU TKO tumor 1
- GSM9116274 TRU TKO tumor 2
- GSM9116275 TRU TKO tumor 3
- GSM9116276 TRU TKO tumor 4
- GSM9116277 TRU TKO tumor 5
Similar datasets
- GSE312096 Inhibition of PAK2 in endothelial cells suppresses tumor angiogenesis and promotes immune sensitization through CXCL10 24 samples
- GSE267542 Tumor intrinsic METTL5 induces immune resistance in ovarian cancer by suppressing ferroptosis 18 samples
- GSE307112 Mapping the Dialogue: Decoding Alveolar Stem-Niche Interactions [I] 886 samples
- GSE260456 DOT1L provides transcriptional memory through PRC1.1 antagonism [RNA-seq] 180 samples
- GSE289193 Histone H4 lysine 20 tri-methylation safeguards breast cancer lineage fidelity and unfolded protein response 160 samples
- GSE270550 Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation [RNA-Seq] 75 samples
- GSE298197 Circulating immune cell signature analysis in HFpEF across species 39 samples
- GSE294887 Individual RNA-seq for different prostate cancer cells, tumors treated by LGK974, ENZ, EPZ6438, EED226 or by CTNNB1 gene knockdown and overexpression, and BRN2 gene knockdown 36 samples
Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.