FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway
Abstract Renal cell carcinoma (RCC) ranks as a prevalent malignant neoplasm, with clear cell renal cell carcinoma (ccRCC, also known as KIRC) accounting for approximately 75% of all RCC cases. The farnesoid X receptor (FXR, encoded by NR1H4), functioning as a nuclear receptor, plays a crucial role i...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-80368-4 |
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| author | Jiachen Liu Shiyu Huang Yanguang Hou Shujie Fu Lei Wang Juncheng Hu Cheng Liu Xiuheng Liu |
| author_facet | Jiachen Liu Shiyu Huang Yanguang Hou Shujie Fu Lei Wang Juncheng Hu Cheng Liu Xiuheng Liu |
| author_sort | Jiachen Liu |
| collection | DOAJ |
| description | Abstract Renal cell carcinoma (RCC) ranks as a prevalent malignant neoplasm, with clear cell renal cell carcinoma (ccRCC, also known as KIRC) accounting for approximately 75% of all RCC cases. The farnesoid X receptor (FXR, encoded by NR1H4), functioning as a nuclear receptor, plays a crucial role in regulating gene transcription. Although the involvement of FXR in tumors of the digestive system and in acute kidney injury has been extensively studied, its specific role in the pathogenesis of ccRCC has yet to be thoroughly investigated. Consequently, the objective of our current investigation is to uncover the functional roles of FXR in ccRCC. In this study, plasmids for the overexpression of FXR were constructed, and small interfering RNA (siRNA) constructs were designed. Dual-luciferase reporter assays confirmed a direct binding interaction between FXR and the promoter of the matrix metalloproteinase 7 (MMP-7) gene. Additionally, a mouse xenograft model elucidated the regulatory effect of FXR on MMP-7 in the context of tumor growth. This study elucidates how FXR regulates the promotion of ccRCC through the MMP-7-mediated EMT pathway. Interestingly, FXR is typically regarded as a tumor suppressor gene that affects gastrointestinal tumors, providing a potential new therapeutic direction for ccRCC. |
| format | Article |
| id | doaj-art-8b12f0d06ed6404f9e1cb4d60f27502c |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-8b12f0d06ed6404f9e1cb4d60f27502c2025-08-20T02:49:09ZengNature PortfolioScientific Reports2045-23222024-11-0114111410.1038/s41598-024-80368-4FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathwayJiachen Liu0Shiyu Huang1Yanguang Hou2Shujie Fu3Lei Wang4Juncheng Hu5Cheng Liu6Xiuheng Liu7Department of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Critical Care Medicine, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityDepartment of Gynecology and Obstetrics, Renmin Hospital of Wuhan UniversityDepartment of Urology, Renmin Hospital of Wuhan UniversityAbstract Renal cell carcinoma (RCC) ranks as a prevalent malignant neoplasm, with clear cell renal cell carcinoma (ccRCC, also known as KIRC) accounting for approximately 75% of all RCC cases. The farnesoid X receptor (FXR, encoded by NR1H4), functioning as a nuclear receptor, plays a crucial role in regulating gene transcription. Although the involvement of FXR in tumors of the digestive system and in acute kidney injury has been extensively studied, its specific role in the pathogenesis of ccRCC has yet to be thoroughly investigated. Consequently, the objective of our current investigation is to uncover the functional roles of FXR in ccRCC. In this study, plasmids for the overexpression of FXR were constructed, and small interfering RNA (siRNA) constructs were designed. Dual-luciferase reporter assays confirmed a direct binding interaction between FXR and the promoter of the matrix metalloproteinase 7 (MMP-7) gene. Additionally, a mouse xenograft model elucidated the regulatory effect of FXR on MMP-7 in the context of tumor growth. This study elucidates how FXR regulates the promotion of ccRCC through the MMP-7-mediated EMT pathway. Interestingly, FXR is typically regarded as a tumor suppressor gene that affects gastrointestinal tumors, providing a potential new therapeutic direction for ccRCC.https://doi.org/10.1038/s41598-024-80368-4FXRMMP-7EMTccRCC |
| spellingShingle | Jiachen Liu Shiyu Huang Yanguang Hou Shujie Fu Lei Wang Juncheng Hu Cheng Liu Xiuheng Liu FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway Scientific Reports FXR MMP-7 EMT ccRCC |
| title | FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway |
| title_full | FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway |
| title_fullStr | FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway |
| title_full_unstemmed | FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway |
| title_short | FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway |
| title_sort | fxr promotes clear cell renal cell carcinoma carcinogenesis via mmp 7 regulated emt pathway |
| topic | FXR MMP-7 EMT ccRCC |
| url | https://doi.org/10.1038/s41598-024-80368-4 |
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