Inhibition of NOS1 promotes the interferon response of melanoma cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35538490", "kind": "science-record", "revision": 2, "content_hash": "sha256:250b211b795057de963fa30e94f8ac911e8f9ffa129e6871a3fd234709f2ebc3", "created_at": "2026-11-01T18:14:26Z", "updated_at": "2026-11-01T18:58:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Inhibition of NOS1 promotes the interferon response of melanoma cells.", "doi": "10.1186/s12967-022-03403-w", "pmid": "35538490", "authors": ["Xi Chen", "Zhiwei Zou", "Qianli Wang", "Wenwen Gao", "Sisi Zeng", "Shuangyan Ye", "Pengfei Xu", "Mengqiu Huang", "Keyi Li", "Jianping Chen", "Zhuo Zhong", "Qianbing Zhang", "Bingtao Hao", "Qiuzhen Liu"], "journal": "Journal of translational medicine", "year": 2022, "abstract": "BACKGROUND: NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown.\nMETHODS: The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. The effect on tumor growth was tested in BALB/c-nu and C57BL/6 mouse models. The gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Genomes) and CLUE GO analysis was done. The clinical data and transcriptional profiles of melanoma patients from the public database TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus, GSE32611) were analyzed by Qlucore Omics Explorer.\nRESULTS: NOS1 deletion suppressed the proliferation of melanoma A375 cells in culture, blocked cell cycling at the G0/G1 phase, and decreased the tumor growth in lung metastasis nodes in a B16 melanoma xenograft mouse model. Moreover, NOS1 knockout increased the infiltration of CD3+ immune cells in tumors. The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion. These DEGs indicated that NOS1 deletion downregulated mostly metabolic functions but upregulated immune response pathways. After inhibiting with NOS1 inhibitor N-PLA, melanoma cells significantly increased the response to IFN[Formula: see text] by upregulation expression of IFN[Formula: see text] simulation genes (ISGs), especially the components in innate immune signaling, JAK-STAT, and TOLL-LIKE pathway. Furthermore, these NOS1-regulating immune genes (NOS1-ISGs) worked as a signature to predict poor overall survival and lower response to chemotherapy in melanoma patients.\nCONCLUSION: These findings provided a transcriptional evidence of NOS1 promotion on tumor growth, which is correlated with metabolic regulation and immune escape in melanoma cells.", "claims": [{"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35538490", "locator": "sections[31] \"notes\" paragraph 1", "quote": "The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35538490", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The transcriptomics analysis identified 2203 differential expression genes (DEGs) after NOS1 deletion.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35538490"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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METHODS: The CRISPR/Cas9 system was used to generate NOS1-knocko"], "order_basis": "paper_text_order:233", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow"], "order_basis": "paper_text_order:378", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["MTT assay, clonogenic assay, EdU assay, and flow cytometric assay. 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Moreover, NOS1 knockout increased the", "ll culture Human melanoma A375 cell line and murine melanoma B16 cell line were maintained in ou"], "order_basis": "paper_text_order:508", "id": "assay:4"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ssion profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of", "gene expression profiles were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyc"], "order_basis": "paper_text_order:571", "id": "assay:5"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were detected with Affymetrix microarray and RNA-seq and KEGG (Kyoto Encyclopedia of Genes and Ge", "ltration of CD3+ immune cells in tumors. 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