CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma
Abstract Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advanc...
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BMC
2025-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03630-9 |
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| author | Kangkang Yang Yushuang Wang Yuli Jian Bo Wang Hao Du Yuqing Xia Jianlei Bi Meihua Guo Zhi Li Ning Wang |
| author_facet | Kangkang Yang Yushuang Wang Yuli Jian Bo Wang Hao Du Yuqing Xia Jianlei Bi Meihua Guo Zhi Li Ning Wang |
| author_sort | Kangkang Yang |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear. Our study developed a risk model utilizing three PANoptosis-associated genes (Caspase 4 (CASP4), TLR3, and CASP5). This model demonstrated a high degree of precision in predicting the prognosis for patients with ccRCC. ccRCC patients in the high-risk group had the strongest immune cell activity, experiencing immune evasion, and might potentially derive advantages from treatment involving combined immune checkpoint inhibitors. CASP5 was highly expressed in ccRCC tissues by RT-qPCR, western blotting, and immunofluorescence. Stable CASP5 knockdown cell lines were constructed by lentivirus in vitro transfection technique. Reducing CASP5 level suppressed the growth, migration, and invasion of ccRCC cells, while encouraging cell apoptosis. In addition, the results of in vivo tumorigenesis experiments showed that down-regulating CASP5 expression inhibited the tumorigenic ability of 786-O cells. Together, the innovative risk model using PANoptosis-associated genes effectively forecasts the tumor microenvironment and survival rates for ccRCC, offering a novel approach to the early, precise diagnosis of ccRCC and the advancement of personalized treatment strategies. |
| format | Article |
| id | doaj-art-92c8940d78434b8db9640baf0eac77c9 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-92c8940d78434b8db9640baf0eac77c92025-01-12T12:40:40ZengBMCCancer Cell International1475-28672025-01-0125111510.1186/s12935-024-03630-9CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinomaKangkang Yang0Yushuang Wang1Yuli Jian2Bo Wang3Hao Du4Yuqing Xia5Jianlei Bi6Meihua Guo7Zhi Li8Ning Wang9Institute for Genome Engineered Animal Models of Human Diseases, National Center of Genetically Engineered Animal Models for International Research, Dalian Medical UniversityDepartment of Clinical Laboratory, Central Hospital of Dalian University of TechnologyLiaoning Provincial Core Lab of Glycobiology and Glycoengineering, College of Basic Medical Sciences, Dalian Medical UniversityDepartment of Clinical Laboratory, Central Hospital of Dalian University of TechnologyDepartment of Urology, Central Hospital of Dalian University of TechnologyPharmaceutical sciences, Massachusetts College of Pharmacy and Health Science UniversityDepartment of Obstetrics and Gynecology, The Second Hospital of Dalian Medical UniversityInstitute for Genome Engineered Animal Models of Human Diseases, National Center of Genetically Engineered Animal Models for International Research, Dalian Medical UniversityDepartment of Clinical Laboratory, Central Hospital of Dalian University of TechnologyInstitute for Genome Engineered Animal Models of Human Diseases, National Center of Genetically Engineered Animal Models for International Research, Dalian Medical UniversityAbstract Clear cell renal cell carcinoma (ccRCC) is a globally severe cancer with an unfavorable prognosis. PANoptosis, a form of cell death regulated by PANoptosomes, plays a role in numerous cancer types. However, the specific roles of genes associated with PANoptosis in the development and advancement of ccRCC remain unclear. Our study developed a risk model utilizing three PANoptosis-associated genes (Caspase 4 (CASP4), TLR3, and CASP5). This model demonstrated a high degree of precision in predicting the prognosis for patients with ccRCC. ccRCC patients in the high-risk group had the strongest immune cell activity, experiencing immune evasion, and might potentially derive advantages from treatment involving combined immune checkpoint inhibitors. CASP5 was highly expressed in ccRCC tissues by RT-qPCR, western blotting, and immunofluorescence. Stable CASP5 knockdown cell lines were constructed by lentivirus in vitro transfection technique. Reducing CASP5 level suppressed the growth, migration, and invasion of ccRCC cells, while encouraging cell apoptosis. In addition, the results of in vivo tumorigenesis experiments showed that down-regulating CASP5 expression inhibited the tumorigenic ability of 786-O cells. Together, the innovative risk model using PANoptosis-associated genes effectively forecasts the tumor microenvironment and survival rates for ccRCC, offering a novel approach to the early, precise diagnosis of ccRCC and the advancement of personalized treatment strategies.https://doi.org/10.1186/s12935-024-03630-9Clear cell renal cell carcinomaPANoptosisCASP5Immune infiltration landscapeRisk model |
| spellingShingle | Kangkang Yang Yushuang Wang Yuli Jian Bo Wang Hao Du Yuqing Xia Jianlei Bi Meihua Guo Zhi Li Ning Wang CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma Cancer Cell International Clear cell renal cell carcinoma PANoptosis CASP5 Immune infiltration landscape Risk model |
| title | CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| title_full | CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| title_fullStr | CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| title_full_unstemmed | CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| title_short | CASP5 associated with PANoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| title_sort | casp5 associated with panoptosis promotes tumorigenesis and progression of clear cell renal cell carcinoma |
| topic | Clear cell renal cell carcinoma PANoptosis CASP5 Immune infiltration landscape Risk model |
| url | https://doi.org/10.1186/s12935-024-03630-9 |
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