Hongsheng Li, Yao Ning, Junjie Yu, Yiju Chen, Qiang He, Juan Jin
{"title":"USP7过表达通过TRIP12去泛素化促进焦亡，从而阻止透明细胞肾细胞癌的进展。","authors":"Hongsheng Li, Yao Ning, Junjie Yu, Yiju Chen, Qiang He, Juan Jin","doi":"10.1080/15384047.2025.2558402","DOIUrl":null,"url":null,"abstract":"<p><p>Ubiquitin-specific protease 7 (USP7) involves in various human cancers due to its capacity for binding and stabilizing specific target proteins through deubiquitylation, but its roles in clear cell renal cell carcinoma (ccRCC) development remains unknown. This study aimed to determine the role of USP7 in the pyroptosis mechanism in ccRCC, thereby providing novel anti-ccRCC strategies. Bioinformatics analysis was conducted to explore the expression of USP7 and TRIP12 in ccRCC patients and their association with patient overall survival. qRT-PCR, western blotting, and ELISA were used to determine the levels of USP7, TRIP12, pyroptosis-related factors. Cell viability, invasion, pyroptosis, and proliferation were evaluated using CCK-8, Transwell, flow cytometry, and immunohistochemistry assays. The direct interaction between USP7 and TRIP12 was validated by co-immunoprecipitation (CO-IP). We found downregulated USP7 in ccRCC tissues, which was related to the shorter patient overall survival (OS). Significantly, USP7 was also decreased in ccRCC cells. oe-USP7 (USP7 overexpression) inhibited ccRCC cell viability, migration, invasion, and enhanced pyroptosis. The caspase-1 specific inhibitor, VX-765, partially abolished the anti-viability, and pro-pyroptosis effects of oe-USP7, indicating USP7 overexpression prevented the malignant phenotype of ccRCC cells by enhancing caspase-1 dependent pyroptosis. Similarly, the shorter patient OS was indicated to be associated with reduced TRIP12 in ccRCC tissues. Besides, oe-USP7 increased TRIP12 expression in ccRCC cells by deubiquitinating TRIP12, while sh-TRIP12 eliminated the biological functions of oe-USP7. The similar effects of oe-USP7 on ccRCC development were found in ccRCC mice. USP7 mediated TRIP12 deubiquitination inhibited ccRCC progression by enhancing pyroptosis.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"26 1","pages":"2558402"},"PeriodicalIF":4.6000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439559/pdf/","citationCount":"0","resultStr":"{\"title\":\"USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination.\",\"authors\":\"Hongsheng Li, Yao Ning, Junjie Yu, Yiju Chen, Qiang He, Juan Jin\",\"doi\":\"10.1080/15384047.2025.2558402\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ubiquitin-specific protease 7 (USP7) involves in various human cancers due to its capacity for binding and stabilizing specific target proteins through deubiquitylation, but its roles in clear cell renal cell carcinoma (ccRCC) development remains unknown. This study aimed to determine the role of USP7 in the pyroptosis mechanism in ccRCC, thereby providing novel anti-ccRCC strategies. Bioinformatics analysis was conducted to explore the expression of USP7 and TRIP12 in ccRCC patients and their association with patient overall survival. qRT-PCR, western blotting, and ELISA were used to determine the levels of USP7, TRIP12, pyroptosis-related factors. Cell viability, invasion, pyroptosis, and proliferation were evaluated using CCK-8, Transwell, flow cytometry, and immunohistochemistry assays. The direct interaction between USP7 and TRIP12 was validated by co-immunoprecipitation (CO-IP). We found downregulated USP7 in ccRCC tissues, which was related to the shorter patient overall survival (OS). Significantly, USP7 was also decreased in ccRCC cells. oe-USP7 (USP7 overexpression) inhibited ccRCC cell viability, migration, invasion, and enhanced pyroptosis. The caspase-1 specific inhibitor, VX-765, partially abolished the anti-viability, and pro-pyroptosis effects of oe-USP7, indicating USP7 overexpression prevented the malignant phenotype of ccRCC cells by enhancing caspase-1 dependent pyroptosis. Similarly, the shorter patient OS was indicated to be associated with reduced TRIP12 in ccRCC tissues. Besides, oe-USP7 increased TRIP12 expression in ccRCC cells by deubiquitinating TRIP12, while sh-TRIP12 eliminated the biological functions of oe-USP7. The similar effects of oe-USP7 on ccRCC development were found in ccRCC mice. 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USP7 overexpression prevents the progression of clear cell renal cell carcinoma by enhancing pyroptosis via TRIP12 deubiquitination.
Ubiquitin-specific protease 7 (USP7) involves in various human cancers due to its capacity for binding and stabilizing specific target proteins through deubiquitylation, but its roles in clear cell renal cell carcinoma (ccRCC) development remains unknown. This study aimed to determine the role of USP7 in the pyroptosis mechanism in ccRCC, thereby providing novel anti-ccRCC strategies. Bioinformatics analysis was conducted to explore the expression of USP7 and TRIP12 in ccRCC patients and their association with patient overall survival. qRT-PCR, western blotting, and ELISA were used to determine the levels of USP7, TRIP12, pyroptosis-related factors. Cell viability, invasion, pyroptosis, and proliferation were evaluated using CCK-8, Transwell, flow cytometry, and immunohistochemistry assays. The direct interaction between USP7 and TRIP12 was validated by co-immunoprecipitation (CO-IP). We found downregulated USP7 in ccRCC tissues, which was related to the shorter patient overall survival (OS). Significantly, USP7 was also decreased in ccRCC cells. oe-USP7 (USP7 overexpression) inhibited ccRCC cell viability, migration, invasion, and enhanced pyroptosis. The caspase-1 specific inhibitor, VX-765, partially abolished the anti-viability, and pro-pyroptosis effects of oe-USP7, indicating USP7 overexpression prevented the malignant phenotype of ccRCC cells by enhancing caspase-1 dependent pyroptosis. Similarly, the shorter patient OS was indicated to be associated with reduced TRIP12 in ccRCC tissues. Besides, oe-USP7 increased TRIP12 expression in ccRCC cells by deubiquitinating TRIP12, while sh-TRIP12 eliminated the biological functions of oe-USP7. The similar effects of oe-USP7 on ccRCC development were found in ccRCC mice. USP7 mediated TRIP12 deubiquitination inhibited ccRCC progression by enhancing pyroptosis.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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