GEO series
Dual function of DOT1L suppresses tumor intrinsic immunogenicity in Hepatocellular carcinoma [RNA-seq]
GSE294355
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
36 samples
Submitted 2026/04/16
Platform GPL24676Platform GPL24247
Summary
Checkpoint inhibitor therapy for Hepatocellular carcinoma (HCC) remains limited in patients’ overall response rate. Discovery and development of more effective combinatorial approaches in HCC checkpoint immunotherapy is urgent. Here, through CPlSPR/Cas9 genetic screens, we identify DOT1L as a versatile epigenetic factor that functions to suppress anti-tumor immunity through a dual mechanism. Depletion of DOT1L induces the expression of transposable elements and subsequent type-I interferon response, and meanwhile lowers ZEB1 levels to further unleash the expression of interferon simulated genes. In turn, we demonstrate that DOT1L loss or treatment with the selective DOT1L inhibitor EPZ-5676 sensitizes tumors to immune checkpoint blockade by increased immune infiltration in mouse. More importantly, EPZ-5676 treatment alone is sufficient to enhance antitumor immunity in humanized mouse model. These findings provide a rationale for targeting DOT1L to improve tumor immunogenicity and overcome immunotherapy resistance.
Published in
Xu S, Gong R, Liu S et al.
· Oncogene 2026
· PMID 41912776
· doi:10.1038/s41388-026-03744-6
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE294355_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 36 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1249077 and SRA study SRP578085. Searching any of these in the dataset finder brings you back here.
Study design
36 conditions, each sampled once — no replicated groups
Read from 36 sample titles: 36 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8902875 HuH-7, sgNeg2_rep1, RNA-seq
- GSM8902876 HuH-7, sgNeg2_rep2, RNA-seq
- GSM8902877 HuH-7, DOT1L_sgRNA#1_rep1, RNA-seq
- GSM8902878 HuH-7, DOT1L_sgRNA#1_rep2, RNA-seq
- GSM8902879 HuH-7, DOT1L_sgRNA#2_rep1, RNA-seq
- GSM8902880 HuH-7, DOT1L_sgRNA#2_rep2, RNA-seq
- GSM8902881 HuH-7, IFN, sgNeg2_rep1, RNA-seq
- GSM8902882 HuH-7, IFN, sgNeg2_rep2, RNA-seq
- GSM8902883 HuH-7, IFN, DOT1L_sgRNA#1_rep1, RNA-seq
- GSM8902884 HuH-7, IFN, DOT1L_sgRNA#1_rep2, RNA-seq
- GSM8902885 HuH-7, IFN, DOT1L_sgRNA#2_rep1, RNA-seq
- GSM8902886 HuH-7, IFN, DOT1L_sgRNA#2_rep2, RNA-seq
- GSM8902887 HuH-7, DMSO_rep1, RNA-seq
- GSM8902888 HuH-7, DMSO_rep2, RNA-seq
- GSM8902889 HuH-7, DMSO_rep3, RNA-seq
- GSM8902890 HuH-7, EPZ-5676_rep1, RNA-seq
- GSM8902891 HuH-7, EPZ-5676_rep2, RNA-seq
- GSM8902892 HuH-7, EPZ-5676_rep3, RNA-seq
- GSM8902893 Hepa1-6, sgNeg2_rep1, RNA-seq
- GSM8902894 Hepa1-6, sgNeg2_rep2, RNA-seq
- GSM8902895 Hepa1-6, Dot1l_sgRNA#1_rep1, RNA-seq
- GSM8902896 Hepa1-6, Dot1l_sgRNA#1_rep2, RNA-seq
- GSM8902897 Hepa1-6, Dot1l_sgRNA#2_rep1, RNA-seq
- GSM8902898 Hepa1-6, Dot1l_sgRNA#2_rep2, RNA-seq
- GSM8902899 Hep53.4, sgNeg2_rep1, RNA-seq
- GSM8902900 Hep53.4, sgNeg2_rep2, RNA-seq
- GSM8902901 Hep53.4, Dot1l_sgRNA#1_rep1, RNA-seq
- GSM8902902 Hep53.4, Dot1l_sgRNA#1_rep2, RNA-seq
- GSM8902903 Hep53.4, Dot1l_sgRNA#2_rep1, RNA-seq
- GSM8902904 Hep53.4, Dot1l_sgRNA#2_rep2, RNA-seq
- GSM8902905 LLC, sgNeg2_rep1, RNA-seq
- GSM8902906 LLC, sgNeg2_rep2, RNA-seq
- GSM8902907 LLC, Dot1l_sgRNA#1_rep1, RNA-seq
- GSM8902908 LLC, Dot1l_sgRNA#1_rep2, RNA-seq
- GSM8902909 LLC, Dot1l_sgRNA#2_rep1, RNA-seq
- GSM8902910 LLC, Dot1l_sgRNA#2_rep2, RNA-seq
Similar datasets
- GSE246221 A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma [RNA-seq] 148 samples
- GSE299215 E7386 enhances lenvatinib’s antitumor activity in preclinical models and human hepatocellular carcinoma. 44 samples
- GSE289625 RNA exonuclease REXO4 resolves m6A-marked R-loops and suppresses anti-tumor immunity [RNAseq] 28 samples
- 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
- GSE260456 DOT1L provides transcriptional memory through PRC1.1 antagonism [RNA-seq] 180 samples
- GSE255108 Targeting CDK7 function in the RNA Polymerase II transcription cycle in inflammatory arthritis 64 samples
- GSE293117 GPR34 loss-of-function rescues TREM2 metabolic dysfunction and promotes responsive microglial states 56 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.