ArticleAmerican journal of translational research2023
ISG15 is a potential therapeutic target for osteosarcoma: a comprehensive analysis based on bioinformatics and in vitro experiments.
Article in American journal of translational research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 1 citations in OpenAlex.
- The ISGylation tapestry in cancer: weaving phenotypic plasticity through multidimensional regulatory looms.Cellular & molecular biology letters · 2025Review
- Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe expression of aberrant interferon-stimulated gene 15 (ISG15) is connected with various human diseases, including cancer. ISG15 is involved in tumor formation and metastasis. However, its role in osteosarcoma is uncertain.
methodsISG15 expression in pan-cancer from RNA Sequencing data were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases. The relationship between ISG15 expression and prognosis was assessed through TCGA clinical survival data. Immunohistochemistry (IHC) images of ISG15 were retrieved using the Human Protein Atlas to analyze the differences in selected normal and tumor tissues. Gene enrichment analysis and signaling pathway analysis were used to assess the potential role of ISG15 in sarcoma, and the correlation between ISG15 expressions and immune cell infiltration levels was estimated by immune infiltration analysis. The expression levels of ISG15 were assessed by qRT-PCR and IHC. Colony formation, wound healing assay and transwell assay were used to detect the effects of ISG15 on the biological behaviors of osteosarcoma cells. The correlation between ISG15 levels and CD8+/CD68+ cells was further examined by double-labeled immunofluorescence. The chemotactic effect of ISG15 on CD8+/CD68+ cells was demonstrated by chemotactic experiments and flow cytometry.
resultsISG15 was highly expressed in most cancers, while high ISG15 expression was significantly correlated with poor overall survival. Gene enrichment analysis in sarcoma suggested that antigen processing and presentation might be involved in the oncogenic mechanism of ISG15. Further immune infiltration analysis showed that high ISG15 expression might reflect the infiltration level of certain immune cells. Additionally, our verification showed that ISG15 was significantly related to the occurrence and metastasis of osteosarcoma, and knockdown of ISG15 significantly altered cell biological behavior, resulting in decreased proliferation, migration and invasion capabilities of osteosarcoma cells. The high expression of ISG15 in osteosarcoma tissue was associated with a high level of CD68+ immune cell infiltration while a low level of CD8+ T cell infiltration. CD68+ immune cells were recruited in vitro by overexpression of ISG15, which on the contrary could weaken the chemotaxis of CD8+ T cells.
conclusionHigh ISG15 expression is an inherent feature of osteosarcoma and triggers tumorigenesis and metastasis by regulating tumor immunogenicity. ISG15 is expected to be the target of osteosarcoma treatment.
Indexed as
Identifiers
36915723PMC10006750W4324129892What OpenQuestion holds
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