TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability
Abstract Background Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy ti...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-022-02583-z |
| _version_ | 1811175696851009536 |
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| author | Xintian Chen Hongmei Yong Miaolei Chen Chuyin Deng Pengfei Wang Sufang Chu Minle Li Pingfu Hou Junnian Zheng Zhongwei Li Jin Bai |
| author_facet | Xintian Chen Hongmei Yong Miaolei Chen Chuyin Deng Pengfei Wang Sufang Chu Minle Li Pingfu Hou Junnian Zheng Zhongwei Li Jin Bai |
| author_sort | Xintian Chen |
| collection | DOAJ |
| description | Abstract Background Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear. Methods The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients. Results TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis. Conclusion The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC. |
| first_indexed | 2024-04-10T19:39:57Z |
| format | Article |
| id | doaj.art-8818b040f3e44e0b9d736d0bee6ff682 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-10T19:39:57Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-8818b040f3e44e0b9d736d0bee6ff6822023-01-29T12:24:43ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662023-01-0142111810.1186/s13046-022-02583-zTRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stabilityXintian Chen0Hongmei Yong1Miaolei Chen2Chuyin Deng3Pengfei Wang4Sufang Chu5Minle Li6Pingfu Hou7Junnian Zheng8Zhongwei Li9Jin Bai10Cancer Institute, Xuzhou Medical UniversityDepartment of Oncology, The Second People’s Hospital of Huai’an, The Affiliated Huai’an Hospital of Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityCancer Institute, Xuzhou Medical UniversityAbstract Background Metabolic reprogramming is a hallmark of various cancers. Targeting metabolic processes is a very attractive treatment for cancer. Renal cell carcinoma (RCC) is a type of metabolic disease, and the lipidomic profile of RCC is significantly altered compared with that of healthy tissue. However, the molecular mechanism underlying lipid metabolism regulation in RCC is not clear. Methods The XF long-chain fatty acid oxidative stress test kits were used to assess the dependence on long-chain fatty acids and mitochondrial function after knockdown TRIM21 in RCC cells. The effect of TRIM21 on the lipid content in RCC cells was determined by metabolomics analysis, Oil Red O staining, and cellular Nile red staining. qRT-PCR and western blot were used to explore the relationship between TRIM21 and lipogenesis, and then the key molecule sterol regulatory element binding transcription factor 1 (SREBF1) was identified to interact with TRIM21 by immunoprecipitation, which was also identified in an orthotopic model. Subsequently, the relevance and clinical significance of TRIM21 and SREBF1 were analyzed by The Cancer Genome Atlas (TCGA) database, and 239 tissues were collected from RCC patients. Results TRIM21 silencing attenuated the dependence of RCC cells on fatty acids, and enhanced lipid accumulation in RCC cells. TRIM21 overexpression significantly decreased lipid contents by decreasing the expression of lipogenic enzymes via ubiquitination-mediated degradation of SREBF1. SREBF1 is critical for TRIM21-mediated lipogenesis inhibition in vitro and in vivo. Moreover, TRIM21 expression is negatively correlated with SREBF1 expression, and TRIM21-SREBF1 is a reliable combinational biomarker for RCC prognosis. Conclusion The findings from this study reveal a novel pathway through which TRIM21 inhibits the lipid metabolism process of RCC and shed light on the development of targeted metabolic treatment and prognosis diagnosis of RCC.https://doi.org/10.1186/s13046-022-02583-zTRIM21LipogenesisSREBF1UbiquitinationRenal cell carcinoma |
| spellingShingle | Xintian Chen Hongmei Yong Miaolei Chen Chuyin Deng Pengfei Wang Sufang Chu Minle Li Pingfu Hou Junnian Zheng Zhongwei Li Jin Bai TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability Journal of Experimental & Clinical Cancer Research TRIM21 Lipogenesis SREBF1 Ubiquitination Renal cell carcinoma |
| title | TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability |
| title_full | TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability |
| title_fullStr | TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability |
| title_full_unstemmed | TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability |
| title_short | TRIM21 attenuates renal carcinoma lipogenesis and malignancy by regulating SREBF1 protein stability |
| title_sort | trim21 attenuates renal carcinoma lipogenesis and malignancy by regulating srebf1 protein stability |
| topic | TRIM21 Lipogenesis SREBF1 Ubiquitination Renal cell carcinoma |
| url | https://doi.org/10.1186/s13046-022-02583-z |
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