CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway
Abstract Background Cancer-associated fibroblasts (CAFs) have been reported to play a significant role in the development and metastasis of various tumors; however, research on their role in promoting prostate cancer (PCa) metastasis under castration conditions remains unclear. Methods In this study...
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BMC
2025-07-01
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| Series: | Biology Direct |
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| Online Access: | https://doi.org/10.1186/s13062-025-00667-2 |
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| author | Xiaodong Song Tiewen Li Wenhao Zhou Chengling Feng Zeng Zhou Yuanming Chen Deng Li Lei Chen Jing Zhao Yu Zhang Bangmin Han |
| author_facet | Xiaodong Song Tiewen Li Wenhao Zhou Chengling Feng Zeng Zhou Yuanming Chen Deng Li Lei Chen Jing Zhao Yu Zhang Bangmin Han |
| author_sort | Xiaodong Song |
| collection | DOAJ |
| description | Abstract Background Cancer-associated fibroblasts (CAFs) have been reported to play a significant role in the development and metastasis of various tumors; however, research on their role in promoting prostate cancer (PCa) metastasis under castration conditions remains unclear. Methods In this study, we utilized quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect the expression differences of microRNA-196b-5p (miR-196b-5p) in the exosomes secreted by CAFs before and after castration. We further characterized the transcriptional regulatory landscape through RNA sequencing combined with bioinformatics databases. In vitro and in vivo experiments were conducted to determine the role of miR-196b-5p in promoting tumor migration and metastasis. The dual-luciferase reporter assay, RT-PCR analysis, and Western blot analysis confirmed that miR-196b-5p targets HOXC8 in prostate cancer. Additionally, transwell assays and Western blot analysis were performed to elucidate the role and specific mechanisms of HOXC8 in tumor metastasis. Results By analyzing the expression differences of miRNAs in the exosomes secreted by CAFs before and after castration, along with relevant data from databases, we found that miR-196b-5p is highly secreted by CAFs after castration. miR-196b-5p promotes the migration and metastasis of prostate cancer cells. Subsequently, through RNA sequencing analysis and experimental validation, we determined that miR-196b-5p targets HOXC8. This interaction activates the NF-κB pathway, leading to the upregulation of epithelial-mesenchymal transition (EMT)-related protein expression, thereby driving the metastasis of prostate cancer. Conclusions Our study elucidates a specific mechanism by which CAF-derived exosomes promote prostate cancer metastasis via miR-196b-5p regulation, contributing to the identification of therapeutic targets for managing tumor metastasis following castration. |
| format | Article |
| id | doaj-art-3192c8649b7e4af495d9d7a572501596 |
| institution | Kabale University |
| issn | 1745-6150 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj-art-3192c8649b7e4af495d9d7a5725015962025-08-20T03:45:19ZengBMCBiology Direct1745-61502025-07-0120112010.1186/s13062-025-00667-2CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathwayXiaodong Song0Tiewen Li1Wenhao Zhou2Chengling Feng3Zeng Zhou4Yuanming Chen5Deng Li6Lei Chen7Jing Zhao8Yu Zhang9Bangmin Han10Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai Fourth People’s Hospital, Tongji University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDapaterment of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South UniversityDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Cancer-associated fibroblasts (CAFs) have been reported to play a significant role in the development and metastasis of various tumors; however, research on their role in promoting prostate cancer (PCa) metastasis under castration conditions remains unclear. Methods In this study, we utilized quantitative reverse transcription polymerase chain reaction (qRT-PCR) to detect the expression differences of microRNA-196b-5p (miR-196b-5p) in the exosomes secreted by CAFs before and after castration. We further characterized the transcriptional regulatory landscape through RNA sequencing combined with bioinformatics databases. In vitro and in vivo experiments were conducted to determine the role of miR-196b-5p in promoting tumor migration and metastasis. The dual-luciferase reporter assay, RT-PCR analysis, and Western blot analysis confirmed that miR-196b-5p targets HOXC8 in prostate cancer. Additionally, transwell assays and Western blot analysis were performed to elucidate the role and specific mechanisms of HOXC8 in tumor metastasis. Results By analyzing the expression differences of miRNAs in the exosomes secreted by CAFs before and after castration, along with relevant data from databases, we found that miR-196b-5p is highly secreted by CAFs after castration. miR-196b-5p promotes the migration and metastasis of prostate cancer cells. Subsequently, through RNA sequencing analysis and experimental validation, we determined that miR-196b-5p targets HOXC8. This interaction activates the NF-κB pathway, leading to the upregulation of epithelial-mesenchymal transition (EMT)-related protein expression, thereby driving the metastasis of prostate cancer. Conclusions Our study elucidates a specific mechanism by which CAF-derived exosomes promote prostate cancer metastasis via miR-196b-5p regulation, contributing to the identification of therapeutic targets for managing tumor metastasis following castration.https://doi.org/10.1186/s13062-025-00667-2Prostate cancerExosomeCancer-associated fibroblastsmiR-196b-5pHOXC8NF-κB |
| spellingShingle | Xiaodong Song Tiewen Li Wenhao Zhou Chengling Feng Zeng Zhou Yuanming Chen Deng Li Lei Chen Jing Zhao Yu Zhang Bangmin Han CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway Biology Direct Prostate cancer Exosome Cancer-associated fibroblasts miR-196b-5p HOXC8 NF-κB |
| title | CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway |
| title_full | CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway |
| title_fullStr | CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway |
| title_full_unstemmed | CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway |
| title_short | CAF-derived exosomal miR-196b-5p after androgen deprivation therapy promotes epithelial-mesenchymal transition in prostate cancer cells through HOXC8/NF-κB signaling pathway |
| title_sort | caf derived exosomal mir 196b 5p after androgen deprivation therapy promotes epithelial mesenchymal transition in prostate cancer cells through hoxc8 nf κb signaling pathway |
| topic | Prostate cancer Exosome Cancer-associated fibroblasts miR-196b-5p HOXC8 NF-κB |
| url | https://doi.org/10.1186/s13062-025-00667-2 |
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