ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
EZH2 Inhibition Enhances PD-L1 Protein Stability Through USP22-Mediated Deubiquitination in Colorectal Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 38 citations in OpenAlex.
- Silencing of USP22 promotes FGF11 degradation to attenuates renal fibrosis in diabetic kidney disease.Renal failure · 2026Article
- Lactate-associated H3K18la upregulates RNF166 to promote immune evasion in hepatocellular carcinoma by remodeling c-Jun ubiquitination.Apoptosis : an international journal on programmed cell death · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- USP10 deubiquitinase: Physiological function, diseases and therapeutic target (Review).International journal of molecular medicine · 2026Review
- Roles of ubiquitin‑specific peptidase 22 in cellular fate: From embryonic survival to tissue repair, inflammation and metabolism (Review).International journal of molecular medicine · 2026Review
- PSMC2 serves as a potential regulatory target of EZH2 in promoting glioma progression via epithelial-mesenchymal transition.Scientific reports · 2026Article
- ZRANB1 depletion inhibits neuroblastoma progression by destabilizing MYCN through EZH2-mediated deubiquitination.Cell biology and toxicology · 2026Article
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Regulation of ferroptosis in colorectal cancer through therapeutic modulation and miRNA targeting.Biochemistry and biophysics reports · 2026Article
- TheJournal of gastrointestinal oncology · 2026Article
- Mutual Exclusion Analysis Shows that DUSP9 Negatively Regulates PD-L1 Expression and Acts as a Target to Enhance Anti-PD-1 Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Crotonate suppresses breast cancer metastasis and promotes immunotherapy response by inducing ACSS2-mediated EZH2-K348 crotonylation.Science advances · 2026Article
- Senescence-associated and immune-related 9p21.3 locus genes in colorectal cancer: epigenetic architecture, molecular landscape and therapeutic possibilities.Frontiers in cell and developmental biology · 2026Review
- Machine learning-based identification of hub genes and prognostic biomarkers in prostate cancer.Frontiers in genetics · 2026Article
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- USP22 knockdown attenuatesFrontiers in neuroscience · 2026Article
- The role of USP19 in human diseases: from molecular function to clinical relevance.Frontiers in immunology · 2026Review
- Decoding the PTM code of cGAS-STING in gastric cancer: from innate DNA sensing to precision combination therapy.Frontiers in immunology · 2026Review
- Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.Cell death & disease · 2025Article
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
The regulation of PD-L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD-L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD-L1 expression and protein stability, and the deubiquitinase ubiquitin-specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD-L1. Importantly, a combination of EZH2 inhibitors with anti-PD-1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD-L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2-USP22-PD-L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor-based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.