ArticleCell reports2023
RNA mis-splicing drives viral mimicry response after DNMTi therapy in SETD2-mutant kidney cancer.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 citations in OpenAlex.
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Distinguishing self from non-self RNA by editing-specific inosine patterns.Nucleic acids research · 2026Article
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Bone marrow immunosuppressive states associate with survival after guadecitabine and atezolizumab therapy in HMA-R/R MDS.Blood neoplasia · 2026Article
- Unveiling the epigenetic landscape: transforming renal cell carcinoma treatment.Clinical epigenetics · 2026Review
- Chromatin Accessibility in Cancer: Biological Functions, Mechanisms, Therapeutic Potential, and Future Directions.MedComm · 2026Review
- Viral mimicry acts as a tumor suppressor in colitis.Nature communications · 2026Article
- Gene-body DNA methylation of ONECUT2 predicts its expression and prostate cancer aggressiveness in needle biopsies.Biomarker research · 2026Article
- Prognostic Role of Global DNA Methylation in Renal Cancer Reveals Decitabine Treatment Benefit.Current medicinal chemistry · 2026Article
- SNAP: Streamlined Nextflow Analysis Pipeline for Immunoprecipitation-Based Epigenomic Profiling of Circulating Chromatin.bioRxiv : the preprint server for biology · 2025Article
- Review
- SETD2 loss-of-function uniquely sensitizes cells to epigenetic targeting of NSD1-directed H3K36 methylation.Genome biology · 2025Article
- Unleashing viral mimicry: A combinatorial strategy to enhance the efficacy of PARP7 inhibitors.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- HIV capsids: orchestrators of innate immune evasion, pathogenesis and pandemicity.The Journal of general virology · 2025Review
- Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy.International journal of biological sciences · 2025Review
- SETD2 and EZH2: Two epigenetic drivers of prostate cancer.Journal of Cancer · 2025Review
- GNAS knockout potentiates HDAC3 inhibition through viral mimicry-related interferon responses in lymphoma.Leukemia · 2024Article
- Combination of PARP and DNA methylation inhibitors as a potential personalized therapy for SETD2-mutated clear-cell renal cancers.Translational andrology and urology · 2024Article
- Mechanisms of DNA Methylation Regulatory Function and Crosstalk with Histone Lysine Methylation.Journal of molecular biology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Tumors with mutations in chromatin regulators present attractive targets for DNA hypomethylating agent 5-aza-2'-deoxycytidine (DAC) therapy, which further disrupts cancer cells' epigenomic fidelity and reactivates transposable element (TE) expression to drive viral mimicry responses. SETD2 encodes a histone methyltransferase (H3K36me3) and is prevalently mutated in advanced kidney cancers. Here, we show that SETD2-mutant kidney cancer cells are especially sensitive in vitro and in vivo to DAC treatment. We find that the viral mimicry response are direct consequences of mis-splicing events, such as exon inclusions or extensions, triggered by DAC treatment in an SETD2-loss context. Comprehensive epigenomic analysis reveals H3K9me3 deposition, rather than DNA methylation dynamics, across intronic TEs might contribute to elevated mis-splicing rates. Through epigenomic and transcriptomic analyses, we show that SETD2-deficient kidney cancers are prone to mis-splicing, which can be therapeutically exacerbated with DAC treatment to increase viral mimicry activation and provide synergy with combinatorial immunotherapy approaches.
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Registered trials
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.