FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression
Abstract Background Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-023-02860-5 |
| _version_ | 1797636615801143296 |
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| author | Wei-Min Hu Ming Li Jin-Zhuo Ning Yu-Qi Tang Tian-Bao Song Lin-Zhi Li Fan Zou Fan Cheng Wei-Min Yu |
| author_facet | Wei-Min Hu Ming Li Jin-Zhuo Ning Yu-Qi Tang Tian-Bao Song Lin-Zhi Li Fan Zou Fan Cheng Wei-Min Yu |
| author_sort | Wei-Min Hu |
| collection | DOAJ |
| description | Abstract Background Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear. Methods In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model. Results FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs. Conclusions In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer. |
| first_indexed | 2024-03-11T12:36:35Z |
| format | Article |
| id | doaj.art-5db473dd92374cee8a7246273d712834 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-03-11T12:36:35Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-5db473dd92374cee8a7246273d7128342023-11-05T12:32:26ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662023-11-0142112110.1186/s13046-023-02860-5FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progressionWei-Min Hu0Ming Li1Jin-Zhuo Ning2Yu-Qi Tang3Tian-Bao Song4Lin-Zhi Li5Fan Zou6Fan Cheng7Wei-Min Yu8Department of Urology, 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 Urology, 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 Urology, Renmin Hospital of Wuhan UniversityAbstract Background Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear. Methods In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model. Results FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs. Conclusions In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.https://doi.org/10.1186/s13046-023-02860-5Bladder cancerCCL2MacrophageVimentin |
| spellingShingle | Wei-Min Hu Ming Li Jin-Zhuo Ning Yu-Qi Tang Tian-Bao Song Lin-Zhi Li Fan Zou Fan Cheng Wei-Min Yu FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression Journal of Experimental & Clinical Cancer Research Bladder cancer CCL2 Macrophage Vimentin |
| title | FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression |
| title_full | FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression |
| title_fullStr | FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression |
| title_full_unstemmed | FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression |
| title_short | FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression |
| title_sort | fam171b stabilizes vimentin and enhances ccl2 mediated tam infiltration to promote bladder cancer progression |
| topic | Bladder cancer CCL2 Macrophage Vimentin |
| url | https://doi.org/10.1186/s13046-023-02860-5 |
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