ArticleJournal of experimental & clinical cancer research : CR2019
NOS1 inhibits the interferon response of cancer cells by S-nitrosylation of HDAC2.
Article in Journal of experimental & clinical cancer research : CR, 2019. 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, 59 citations in OpenAlex.
- S-nitrosylation topology in melanoma: established mechanisms, unresolved redox-immune links, and a testable framework.Redox biology · 2026Review
- Oligodendrocyte-Targeted SGK1.1 Inhibition Alleviates White Matter Injury and Cognitive Impairment in Alzheimer's Disease via Modulation of HDAC2 Phosphorylation.CNS neuroscience & therapeutics · 2026Article
- NAT10-Mediated ac4C Modification of circANKRD12 Reprograms the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- S-nitrosylation of IRF7 induced by NOS1 expression in melanoma suppresses anti-tumor immunity.Cell death & disease · 2026Article
- The recurrence or metastasis related gene predicts the prognosis of extremity and trunk soft tissue sarcoma.Precision clinical medicine · 2025Article
- S-Nitrosylation of p53 in Melanoma Cells Under Nitrosative Stress.International journal of molecular sciences · 2025Article
- Nitric oxide synthase 1 inhibits the progression of esophageal cancer through interacting with nitric oxide synthase 1 adaptor protein.World journal of gastrointestinal oncology · 2025Article
- The evolution of S-nitrosylation detection methodology and the role of protein S-nitrosylation in various cancers.Cancer cell international · 2024Review
- KDM3A Ablation Activates Endogenous Retrovirus Expression to Stimulate Antitumor Immunity in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Boosting immunity: synergistic antiviral effects of luteolin, vitamin C, magnesium and zinc against SARS-CoV-2 3CLpro.Bioscience reports · 2024Article
- Review
- Screening of co-expressed genes in hypopharyngeal carcinoma with esophageal carcinoma based on RNA sequencing and Clinical Research.Scientific reports · 2024Article
- Host factors of SARS-CoV-2 in infection, pathogenesis, and long-term effects.Frontiers in cellular and infection microbiology · 2024Review
- A metabolic perspective on nitric oxide function in melanoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Assessment of 13 essential and toxic trace elements in tumor and peritumoral brain tissues from human glioblastoma.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Epigenetic perspectives associated with COVID-19 infection and related cytokine storm: an updated review.Infection · 2023Review
- ARL-17477 is a dual inhibitor of NOS1 and the autophagic-lysosomal system that prevents tumor growth in vitro and in vivo.Scientific reports · 2023Article
- Antitarget, Anti-SARS-CoV-2 Leads, Drugs, and the Drug Discovery-Genetics Alliance Perspective.Journal of medicinal chemistry · 2023Review
- Involvement of epigenetics in affecting host immunity during SARS-CoV-2 infection.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.International immunopharmacology · 2022Review
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe dysfunction of type I interferon (IFN) signaling is an important mechanism of immune escape and metastasis in tumors. Increased NOS1 expression has been detected in melanoma, which correlated with dysfunctional IFN signaling and poor response to immunotherapy, but the specific mechanism has not been determined. In this study, we investigated the regulation of NOS1 on the interferon response and clarified the relevant molecular mechanisms.
methodsAfter stable transfection of A375 cells with NOS1 expression plasmids, the transcription and expression of IFNα-stimulated genes (ISGs) were assessed using pISRE luciferase reporter gene analysis, RT-PCR, and western blotting, respectively. The effect of NOS1 on lung metastasis was assessed in melanoma mouse models. A biotin-switch assay was performed to detect the S-nitrosylation of HDAC2 by NOS1. ChIP-qPCR was conducted to measure the binding of HDAC2, H4K16ac, H4K5ac, H3ac, and RNA polymerase II in the promoters of ISGs after IFNα stimulation. This effect was further evaluated by altering the expression level of HDAC2 or by transfecting the HDAC2-C262A/C274A site mutant plasmids into cells. The coimmunoprecipitation assay was performed to detect the interaction of HDAC2 with STAT1 and STAT2. Loss-of-function and gain-of-function approaches were used to examine the effect of HDAC2-C262A/C274A on lung metastasis. Tumor infiltrating lymphocytes were analyzed by flow cytometry.
resultsHDAC2 is recruited to the promoter of ISGs and deacetylates H4K16 for the optimal expression of ISGs in response to IFNα treatment. Overexpression of NOS1 in melanoma cells decreases IFNα-responsiveness and induces the S-nitrosylation of HDAC2-C262/C274. This modification decreases the binding of HDAC2 with STAT1, thereby reducing the recruitment of HDAC2 to the ISG promoter and the deacetylation of H4K16. Moreover, expression of a mutant form of HDAC2, which cannot be nitrosylated, reverses the inhibition of ISG expression by NOS1 in vitro and decreases NOS1-induced lung metastasis and inhibition of tumor infiltrating lymphocytes in a melanoma mouse model.
conclusionsThis study provides evidence that NOS1 induces dysfunctional IFN signaling to promote lung metastasis in melanoma, highlighting NOS1-induced S-nitrosylation of HDAC2 in the regulation of IFN signaling via histone modification.
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