ArticleClinical and translational medicine2024
Inhibition of HDAC2 sensitises antitumour therapy by promoting NLRP3/GSDMD-mediated pyroptosis in colorectal cancer.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Synergistic mechanisms and clinical translation of regorafenib combination therapies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- PCBP2 mediates MTUS1 degradation through 3'-UTR binding to restrict pyroptosis and augment malignant progression in esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2026Article
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- Pyroptosis as a double-edged sword in colorectal cancer: Molecular mechanisms and therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- Anti-Colorectal Cancer Mechanisms of Natural Saponins: Advances and Therapeutic Implications.Chinese journal of integrative medicine · 2026Review
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Molecular mechanisms of NLRP3 inflammasome activation.Experimental & molecular medicine · 2026Review
- The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.MedComm · 2026Review
- Peroxiredoxin 1 as a novel pyroptosis inducer in colorectal cancer: Insights and future directions.World journal of gastroenterology · 2026Article
- Advances in the research of gasdermin-dependent pyroptosis mechanisms and therapeutic targets in inflammatory diseases.Apoptosis : an international journal on programmed cell death · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Regulation of apoptosis, ferroptosis, and pyroptosis mediated by acetylation.Cell death discovery · 2026Review
- Epigenetic regulation of PANoptosis: DNA methylation, histone modifications and non-coding RNAs.EXCLI journal · 2026Review
- Epigenetic regulation of the β-catenin pathway in cadmium-induced colorectal cancer progression and chemoresistance.Frontiers in cell and developmental biology · 2026Review
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Comparative Efficacy of Triamcinolone versus Dexamethasone in Local Injection for Stenosing Tenosynovitis of the Metacarpophalangeal Joint: A Retrospective Cohort Study.Drug design, development and therapy · 2026Article
- Organelles and cancer cell pyroptosis: overview and perspectives.Cell death & disease · 2025Review
- HDAC2 as a therapeutic target in bladder cancer: insights into the altered epigenetic regulation and lysine lactylation.Journal of experimental & clinical cancer research : CR · 2025Article
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17 authors.
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Abstract
backgroundAlthough numerous studies have indicated that activated pyroptosis can enhance the efficacy of antitumour therapy in several tumours, the precise mechanism of pyroptosis in colorectal cancer (CRC) remains unclear.
methodsPyroptosis in CRC cells treated with antitumour agents was assessed using various techniques, including Western blotting, lactate dehydrogenase release assay and microscopy analysis. To uncover the epigenetic mechanisms that regulate NLRP3, chromatin changes and NLRP3 promoter histone modifications were assessed using Assay for Transposase-Accessible Chromatin using sequencing and RNA sequencing. Chromatin immunoprecipitation‒quantitative polymerase chain reaction was used to investigate the NLRP3 transcriptional regulatory mechanism. Additionally, xenograft and patient-derived xenograft models were constructed to validate the effects of the drug combinations.
resultsAs the core molecule of the inflammasome, NLRP3 expression was silenced in CRC, thereby limiting gasdermin D (GSDMD)-mediated pyroptosis. Supplementation with NLRP3 can rescue pyroptosis induced by antitumour therapy. Overexpression of HDAC2 in CRC silences NLRP3 via epigenetic regulation. Mechanistically, HDAC2 suppressed chromatin accessibility by eliminating H3K27 acetylation. HDAC2 knockout promotes H3K27ac-mediated recruitment of the BRD4-p-P65 complex to enhance NLRP3 transcription. Inhibiting HDAC2 by Santacruzamate A in combination with classic antitumour agents (5-fluorouracil or regorafenib) in CRC xenograft-bearing animals markedly activated pyroptosis and achieved a significant therapeutic effect. Clinically, HDAC2 is inversely correlated with H3K27ac/p-P65/NLRP3 and is a prognostic factor for CRC patients.
conclusionCollectively, our data revealed a crucial role for HDAC2 in inhibiting NLRP3/GSDMD-mediated pyroptosis in CRC cells and highlighted HDAC2 as a potential therapeutic target for antitumour therapy. HIGHLIGHTS: Silencing of NLRP3 limits the GSDMD-dependent pyroptosis in colorectal cancer. HDAC2-mediated histone deacetylation leads to epigenetic silencing of NLRP3. HDAC2 suppresses the NLRP3 transcription by inhibiting the formation of H3K27ac/BRD4/p-P65 complex. Targeting HDAC2 activates pyroptosis and enhances therapeutic effect.
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