ArticleProceedings of the National Academy of Sciences of the United States of America2022
NOS2 and
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 58 citations in OpenAlex.
- Integrated network pharmacology, molecular simulations, biophysical validation, and experimental validation to reveal the pharmacological effects and targets of Senkyunolide A against inflammation and oxidative stress.BMC complementary medicine and therapies · 2026Article
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- Optimized derivation and culture system of human naïve pluripotent stem cells with enhanced DNA methylation status and genomic stability.Protein & cell · 2025Article
- Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome.Nature communications · 2025Article
- Inflammaging and Brain Aging.International journal of molecular sciences · 2024Review
- Deconvoluting nitric oxide-protein interactions with spatially resolved multiplex imaging.Chemical science · 2024Article
- Nitric oxide inhibits ten-eleven translocation DNA demethylases to regulate 5mC and 5hmC across the genome.Research square · 2024Article
- Epigenetic Approaches to Identifying Asthma Endotypes.Allergy, asthma & immunology research · 2024Review
- Unveiling the potent effect of vitamin D: harnessing Nrf2/HO-1 signaling pathways as molecular targets to alleviate urban particulate matter-induced asthma inflammation.BMC pulmonary medicine · 2024Article
- The Advances in the Development of Epigenetic Modifications Therapeutic Drugs Delivery Systems.International journal of nanomedicine · 2024Review
- G6PD Orchestrates Genome-Wide DNA Methylation and Gene Expression in the Vascular Wall.International journal of molecular sciences · 2023Article
- Chronic inflammation and the hallmarks of aging.Molecular metabolism · 2023Review
- The Mechanism of DNA Methylation and miRNA in Breast Cancer.International journal of molecular sciences · 2023Review
- Article
- Pivotal role for S-nitrosylation of DNA methyltransferase 3B in epigenetic regulation of tumorigenesis.Nature communications · 2023Article
- Thioredoxin 1 promotes autophagy through transnitrosylation of Atg7 during myocardial ischemia.The Journal of clinical investigation · 2023Article
- RNA interference-mediated silencing of DNA methyltransferase 1 attenuates neuropathic pain by accelerating microglia M2 polarization.BMC neurology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Inducible nitric oxide synthase (NOS2) produces high local concentrations of nitric oxide (NO), and its expression is associated with inflammation, cellular stress signals, and cellular transformation. Additionally, NOS2 expression results in aggressive cancer cell phenotypes and is correlated with poor outcomes in patients with breast cancer. DNA hypomethylation, especially of noncoding repeat elements, is an early event in carcinogenesis and is a common feature of cancer cells. In addition to altered gene expression, DNA hypomethylation results in genomic instability via retrotransposon activation. Here, we show that NOS2 expression and associated NO signaling results in substantial DNA hypomethylation in human cell lines by inducing the degradation of DNA (cytosine-5)–methyltransferase 1 (DNMT1) protein. Similarly, NOS2 expression levels were correlated with decreased DNA methylation in human breast tumors. NOS2 expression and NO signaling also resulted in long interspersed noncoding element 1 (LINE-1) retrotransposon hypomethylation, expression, and DNA damage. DNMT1 degradation was mediated by an NO/p38-MAPK/lysine acetyltransferase 5–dependent mechanism. Furthermore, we show that this mechanism is required for NO-mediated epithelial transformation. Therefore, we conclude that NOS2 and NO signaling results in DNA damage and malignant cellular transformation via an epigenetic mechanism.
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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.