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ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer

Augmentation of endogenous double-stranded RNA (dsRNA) has become a promising strategy for activating anti-tumor immunity through induction of type I interferon (IFN) in the treatment of ovarian carcinoma. However, the underlying regulatory mechanisms of dsRNA in ovarian carcinoma remain elusive. Fr...

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Autores principales: Chen, Zhigao, Yin, Min, Jia, Haixue, Chen, Qian, Zhang, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10277467/
https://www.ncbi.nlm.nih.gov/pubmed/37342328
http://dx.doi.org/10.3389/fimmu.2023.1176103
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author Chen, Zhigao
Yin, Min
Jia, Haixue
Chen, Qian
Zhang, Hongbing
author_facet Chen, Zhigao
Yin, Min
Jia, Haixue
Chen, Qian
Zhang, Hongbing
author_sort Chen, Zhigao
collection PubMed
description Augmentation of endogenous double-stranded RNA (dsRNA) has become a promising strategy for activating anti-tumor immunity through induction of type I interferon (IFN) in the treatment of ovarian carcinoma. However, the underlying regulatory mechanisms of dsRNA in ovarian carcinoma remain elusive. From The Cancer Genome Atlas (TCGA), we downloaded RNA expression profiles and clinical data of patients with ovarian carcinoma. Using the consensus clustering method, patients can be classified by their expression level of core interferon-stimulated genes (ISGs): IFN signatures high and IFN signatures low. The IFN signatures high group had a good prognosis. Gene set enrichment analysis (GSEA) showed that differentially expressed genes (DEGs) were primarily associated with anti-foreign immune responses. Based on results from protein-protein interaction (PPI) networks and survival analysis, ISG20 was identified as a key gene involved in host anti-tumor immune response. Further, elevated ISG20 expression in ovarian cancer cells led to increased IFN-β production. The elevated interferon improved the immunogenicity of tumor cells and generated chemokines that attract immune cells to infiltrate the area. Upon overexpression of ISG20, endogenous dsRNA accumulated in the cell and stimulated IFN-β production through the Retinoic acid-inducible gene I (RIG-I)-mediated dsRNA sense pathway. The accumulation of dsRNA was associated with the ribonuclease activity of ISG20. This study suggests that targeting ISG20 is a potential immune therapeutic approach to treat ovarian cancer.
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spelling pubmed-102774672023-06-20 ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer Chen, Zhigao Yin, Min Jia, Haixue Chen, Qian Zhang, Hongbing Front Immunol Immunology Augmentation of endogenous double-stranded RNA (dsRNA) has become a promising strategy for activating anti-tumor immunity through induction of type I interferon (IFN) in the treatment of ovarian carcinoma. However, the underlying regulatory mechanisms of dsRNA in ovarian carcinoma remain elusive. From The Cancer Genome Atlas (TCGA), we downloaded RNA expression profiles and clinical data of patients with ovarian carcinoma. Using the consensus clustering method, patients can be classified by their expression level of core interferon-stimulated genes (ISGs): IFN signatures high and IFN signatures low. The IFN signatures high group had a good prognosis. Gene set enrichment analysis (GSEA) showed that differentially expressed genes (DEGs) were primarily associated with anti-foreign immune responses. Based on results from protein-protein interaction (PPI) networks and survival analysis, ISG20 was identified as a key gene involved in host anti-tumor immune response. Further, elevated ISG20 expression in ovarian cancer cells led to increased IFN-β production. The elevated interferon improved the immunogenicity of tumor cells and generated chemokines that attract immune cells to infiltrate the area. Upon overexpression of ISG20, endogenous dsRNA accumulated in the cell and stimulated IFN-β production through the Retinoic acid-inducible gene I (RIG-I)-mediated dsRNA sense pathway. The accumulation of dsRNA was associated with the ribonuclease activity of ISG20. This study suggests that targeting ISG20 is a potential immune therapeutic approach to treat ovarian cancer. Frontiers Media S.A. 2023-06-05 /pmc/articles/PMC10277467/ /pubmed/37342328 http://dx.doi.org/10.3389/fimmu.2023.1176103 Text en Copyright © 2023 Chen, Yin, Jia, Chen and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Chen, Zhigao
Yin, Min
Jia, Haixue
Chen, Qian
Zhang, Hongbing
ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title_full ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title_fullStr ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title_full_unstemmed ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title_short ISG20 stimulates anti-tumor immunity via a double-stranded RNA-induced interferon response in ovarian cancer
title_sort isg20 stimulates anti-tumor immunity via a double-stranded rna-induced interferon response in ovarian cancer
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10277467/
https://www.ncbi.nlm.nih.gov/pubmed/37342328
http://dx.doi.org/10.3389/fimmu.2023.1176103
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