ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Zebularine elevates STING expression and enhances cGAMP cancer immunotherapy in mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. 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, 54 citations in OpenAlex.
- The cGAS-STING Pathway: A Double-Edged Regulator of Neuroinflammation and Myelin Regeneration.Molecular neurobiology · 2026Review
- Discovery of XNW5004 as a novel EZH2 inhibitor that enhances anti-tumor immunity and synergizes with PD-1 blockade immunotherapy in lung adenocarcinoma.Journal of translational medicine · 2026Article
- DHRS9 generates crotonyl-CoA from butyryl-CoA to epigenetically regulate STING transcription and potentiate immune activation.Cell death and differentiation · 2026Article
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- PCBP1 binding to single-stranded poly-cytosine motifs enhances cGAS sensing and impairs breast cancer development.Communications biology · 2026Article
- Modular engineered outer membrane vesicles for synergistic cancer immunotherapy via PD-L1 blockade and epigenetic reprogramming.Frontiers in immunology · 2026Article
- Decoding the PTM code of cGAS-STING in gastric cancer: from innate DNA sensing to precision combination therapy.Frontiers in immunology · 2026Review
- Targeting the cGAS-STING Pathway in Gastrointestinal Cancers: Modulating Tumor-associated Inflammation for Therapeutic Effect.Current drug targets · 2026Review
- Microbiota-driven metabolic-immune crosstalk in breast cancer.Frontiers in pharmacology · 2026Review
- Targeting chaperone-mediated autophagy inhibits properties of glioblastoma stem cells and restores anti-tumor immunity.Nature communications · 2025Article
- cGAS-STING signaling in melanoma: regulation and therapeutic targeting.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Immunotherapy resistance in non-small cell lung cancer: from mechanisms to therapeutic opportunities.Journal of experimental & clinical cancer research : CR · 2025Review
- Dynamic STING repression orchestrates immune cell development and function.Science immunology · 2025Article
- Article
- Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Deciphering the Role of Oroxylin A in Liver Fibrosis.Drug design, development and therapy · 2025Review
- Current trends in sensitizing immune checkpoint inhibitors for cancer treatment.Molecular cancer · 2024Review
- cGAS/STING in skin melanoma: from molecular mechanisms to therapeutics.Cell communication and signaling : CCS · 2024Review
- Tumor microenvironment-responsive manganese-based nano-modulator activate the cGAS-STING pathway to enhance innate immune system response.Journal of nanobiotechnology · 2024Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA methylation abnormality is closely related to tumor occurrence and development. Chemical inhibitors targeting DNA methyltransferase (DNMTis) have been used in treating cancer. However, the impact of DNMTis on antitumor immunity has not been well elucidated. In this study, we show that zebularine (a demethylating agent) treatment of cancer cells led to increased levels of interferon response in a cyclic guanosine monophosphate-AMP (cGAMP) synthase (cGAS)- and stimulator of interferon genes (STING)-dependent manner. This treatment also specifically sensitized the cGAS-STING pathway in response to DNA stimulation. Incorporation of zebularine into genomic DNA caused demethylation and elevated expression of a group of genes, including STING. Without causing DNA damage, zebularine led to accumulation of DNA species in the cytoplasm of treated cells. In syngeneic tumor models, administration of zebularine alone reduced tumor burden and extended mice survival. This effect synergized with cGAMP and immune checkpoint blockade therapy. The efficacy of zebularine was abolished in nude mice and in cGAS
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