{"title":"泛素特异性肽酶20通过调节前列腺素E2在结直肠癌腹腔内转移模型中影响免疫细胞浸润。","authors":"Yang Hua, Xiukun Ma, Xinyu Zhao, Xiaomeng Wei, Xiaojing Mu, Botao Wang, Xiangfei Yuan","doi":"10.21037/tcr-2024-2194","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ubiquitin-specific peptidase 20 (USP20) acts as oncogene or tumor suppressor gene in different types of cancer. But there are only a few reports about the effect of USP20 on colorectal cancer (CRC). This study aims to further explore the novel molecular mechanisms of USP20 in intraperitoneal metastasis of CRC.</p><p><strong>Methods: </strong>First, bioinformatics analyses were performed to discover the association between USP20 expression and the clinical characteristics of CRC. Subsequently, the mouse model was constructed using a USP20 knockout (USP20-KO) colon cell line to validate the effects of USP20 on intraperitoneal metastasis and immune cell infiltration. And then metabolomics study was performed on the USP20-KO cells to find the novel mechanisms of USP20. Finally, the relationship of prostaglandin E2 (PGE2) and USP20 was identified by enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments.</p><p><strong>Results: </strong>Bioinformatics analyses showed that the USP20 expression was significantly upregulated in CRC and affected immune cell infiltration. The animal model study revealed that the intraperitoneal metastasis of tumor cell was inhibited by knocking out USP20, and the expression of USP20 could affect the proportions of CD8<sup>+</sup> T cells and myeloid-derived suppressor cells (MDSCs) in tumor tissue and ascites. Metabolomics study found that PGE2 should be the key metabolite regulated by USP20 for affecting immune cell infiltration. Finally, it was validated that the expressions of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and microsomal prostaglandin E synthase-1 (mPGES-1) were regulated by the USP20 related ubiquitin-proteasome pathway.</p><p><strong>Conclusions: </strong>The USP20 expression is significantly upregulated in CRC, and can promote tumor metastasis by affecting immune cell infiltration. As an important tumor metabolite which can influence immune cell infiltration, PGE2 is regulated by USP20 through the protein degradation of mPGES-1 and 15-PGDH mediated by proteasome.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 5","pages":"3149-3160"},"PeriodicalIF":1.5000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170121/pdf/","citationCount":"0","resultStr":"{\"title\":\"Ubiquitin-specific peptidase 20 affects immune cell infiltration by regulating prostaglandin E2 on intraperitoneal metastasis model of colorectal cancer.\",\"authors\":\"Yang Hua, Xiukun Ma, Xinyu Zhao, Xiaomeng Wei, Xiaojing Mu, Botao Wang, Xiangfei Yuan\",\"doi\":\"10.21037/tcr-2024-2194\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Ubiquitin-specific peptidase 20 (USP20) acts as oncogene or tumor suppressor gene in different types of cancer. But there are only a few reports about the effect of USP20 on colorectal cancer (CRC). This study aims to further explore the novel molecular mechanisms of USP20 in intraperitoneal metastasis of CRC.</p><p><strong>Methods: </strong>First, bioinformatics analyses were performed to discover the association between USP20 expression and the clinical characteristics of CRC. Subsequently, the mouse model was constructed using a USP20 knockout (USP20-KO) colon cell line to validate the effects of USP20 on intraperitoneal metastasis and immune cell infiltration. And then metabolomics study was performed on the USP20-KO cells to find the novel mechanisms of USP20. Finally, the relationship of prostaglandin E2 (PGE2) and USP20 was identified by enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments.</p><p><strong>Results: </strong>Bioinformatics analyses showed that the USP20 expression was significantly upregulated in CRC and affected immune cell infiltration. The animal model study revealed that the intraperitoneal metastasis of tumor cell was inhibited by knocking out USP20, and the expression of USP20 could affect the proportions of CD8<sup>+</sup> T cells and myeloid-derived suppressor cells (MDSCs) in tumor tissue and ascites. Metabolomics study found that PGE2 should be the key metabolite regulated by USP20 for affecting immune cell infiltration. Finally, it was validated that the expressions of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and microsomal prostaglandin E synthase-1 (mPGES-1) were regulated by the USP20 related ubiquitin-proteasome pathway.</p><p><strong>Conclusions: </strong>The USP20 expression is significantly upregulated in CRC, and can promote tumor metastasis by affecting immune cell infiltration. As an important tumor metabolite which can influence immune cell infiltration, PGE2 is regulated by USP20 through the protein degradation of mPGES-1 and 15-PGDH mediated by proteasome.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"14 5\",\"pages\":\"3149-3160\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2025-05-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12170121/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-2024-2194\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2024-2194","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/16 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
Ubiquitin-specific peptidase 20 affects immune cell infiltration by regulating prostaglandin E2 on intraperitoneal metastasis model of colorectal cancer.
Background: Ubiquitin-specific peptidase 20 (USP20) acts as oncogene or tumor suppressor gene in different types of cancer. But there are only a few reports about the effect of USP20 on colorectal cancer (CRC). This study aims to further explore the novel molecular mechanisms of USP20 in intraperitoneal metastasis of CRC.
Methods: First, bioinformatics analyses were performed to discover the association between USP20 expression and the clinical characteristics of CRC. Subsequently, the mouse model was constructed using a USP20 knockout (USP20-KO) colon cell line to validate the effects of USP20 on intraperitoneal metastasis and immune cell infiltration. And then metabolomics study was performed on the USP20-KO cells to find the novel mechanisms of USP20. Finally, the relationship of prostaglandin E2 (PGE2) and USP20 was identified by enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments.
Results: Bioinformatics analyses showed that the USP20 expression was significantly upregulated in CRC and affected immune cell infiltration. The animal model study revealed that the intraperitoneal metastasis of tumor cell was inhibited by knocking out USP20, and the expression of USP20 could affect the proportions of CD8+ T cells and myeloid-derived suppressor cells (MDSCs) in tumor tissue and ascites. Metabolomics study found that PGE2 should be the key metabolite regulated by USP20 for affecting immune cell infiltration. Finally, it was validated that the expressions of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and microsomal prostaglandin E synthase-1 (mPGES-1) were regulated by the USP20 related ubiquitin-proteasome pathway.
Conclusions: The USP20 expression is significantly upregulated in CRC, and can promote tumor metastasis by affecting immune cell infiltration. As an important tumor metabolite which can influence immune cell infiltration, PGE2 is regulated by USP20 through the protein degradation of mPGES-1 and 15-PGDH mediated by proteasome.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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