Inhibition of NOS1 promotes the interferon response of melanoma cells

• DOI: 10.1186/s12967-022-03403-w
• Publication Date: 2022-05-10T13:03:52Z
• 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
• Keywords: Bioinformatics; Immunology; Melanoma, Experimental; 610; Nitric Oxide Synthase Type I; Inbred C57BL; Medical and Health Sciences; Experimental; Mice; 03 medical and health sciences; Genetics; 2.1 Biological and endogenous factors; Animals; Humans; Aetiology; CRISPR/Cas9; Melanoma; Cancer; Neoplastic; 0303 health sciences; Research; Gene Expression Profiling; Human Genome; R; 3. Good health; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Metabolism; Gene Expression Regulation; Interferon; Medicine; Interferons; NOS1; Biotechnology

Abstract Background NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of type I IFN response and immune escape melanoma is still unknown. Methods The CRISPR/Cas9 system was used to generate NOS1-knockout cells biological characteristics were evaluated by MTT assay, clonogenic EdU flow cytometric assay. effect on tumor growth tested BALB/c-nu C57BL/6 mouse models. gene profiles detected Affymetrix microarray RNA-seq KEGG (Kyoto Encyclopedia Genes Genomes) CLUE GO analysis done. clinical data transcriptional from public database TCGA (The Cancer Genome Atlas) GEO (Gene Expression Omnibus, GSE32611) analyzed Qlucore Omics Explorer. Results deletion suppressed proliferation A375 culture, blocked cell cycling at G0/G1 phase, decreased lung metastasis nodes a B16 xenograft model. Moreover, knockout increased infiltration CD3+ tumors. transcriptomics identified 2203 differential genes (DEGs) after deletion. These DEGs indicated that downregulated mostly metabolic functions but upregulated pathways. After inhibiting inhibitor N-PLA, significantly $$\upalpha $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>α</mml:mi> </mml:math> upregulation simulation (ISGs), especially components innate signaling, JAK-STAT, TOLL-LIKE pathway. Furthermore, these NOS1-regulating (NOS1-ISGs) worked as signature predict overall survival lower chemotherapy patients. Conclusion findings provided evidence promotion growth, which correlated regulation cells.