The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells
Abstract Background Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate‐specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ‐confined tumors. A...
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Wiley
2024-08-01
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| Online Access: | https://doi.org/10.1002/cam4.70106 |
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| author | Chieh Huo Ying‐Yu Kuo Ching‐Yu Lin Shine‐Gwo Shiah Chia‐Yang Li Shu‐Pin Huang Jen‐Kun Chen Wen‐Ching Wang Hsing‐Jien Kung Chih‐Pin Chuu |
| author_facet | Chieh Huo Ying‐Yu Kuo Ching‐Yu Lin Shine‐Gwo Shiah Chia‐Yang Li Shu‐Pin Huang Jen‐Kun Chen Wen‐Ching Wang Hsing‐Jien Kung Chih‐Pin Chuu |
| author_sort | Chieh Huo |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate‐specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ‐confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. Methods The PC‐3AR (PC‐3 cells re‐expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound‐healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro‐Western Array, co‐immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. Results In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho‐AR Ser81 and yes‐associated protein 1 (YAP), decreased phospho‐YAP Ser217, and altered epithelial‐mesenchymal transition (EMT) proteins in PCa cells. Co‐IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen‐induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa‐miR‐5001‐5p but increased hsa‐miR‐203a and hsa‐miR‐210‐3p in PC‐3AR cells but not PC‐3 cells. Treatment with inhibitors targeting hsa‐miR‐203a/hsa‐miR‐210‐3p, or overexpression of hsa‐miR‐5001‐5p decreased YAP expression as well as suppressed the androgen‐induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has‐miR‐210‐3p in the presence of androgen. Conclusions Our observations indicated that miRNAs 203a/210‐3p/5001‐5p regulate the androgen/AR/YAP‐induced PCa metastasis. |
| format | Article |
| id | doaj-art-39ea7ea40a3a452fa6a80b7de7df3a9c |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-39ea7ea40a3a452fa6a80b7de7df3a9c2025-08-20T02:48:12ZengWileyCancer Medicine2045-76342024-08-011316n/an/a10.1002/cam4.70106The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cellsChieh Huo0Ying‐Yu Kuo1Ching‐Yu Lin2Shine‐Gwo Shiah3Chia‐Yang Li4Shu‐Pin Huang5Jen‐Kun Chen6Wen‐Ching Wang7Hsing‐Jien Kung8Chih‐Pin Chuu9Institute of Cellular and System Medicine National Health Research Institutes Zhunan TaiwanInstitute of Cellular and System Medicine National Health Research Institutes Zhunan TaiwanInstitute of Cellular and System Medicine National Health Research Institutes Zhunan TaiwanNational Institute of Cancer Research National Health Research Institutes Zhunan TaiwanGraduate Institute of Medicine, College of Medicine Kaohsiung Medical University Kaohsiung TaiwanDepartment of Urology, School of Medicine, College of Medicine Kaohsiung Medical University Kaohsiung TaiwanInstitute of Biomedical Engineering and Nanomedicine National Health Research Institutes Zhunan TaiwanInstitute of Molecular and Cellular Biology National Tsing Hua University Hsinchu TaiwanPh.D. Program for Cancer Molecular Biology and Drug Discovery Taipei Medical University Taipei TaiwanInstitute of Cellular and System Medicine National Health Research Institutes Zhunan TaiwanAbstract Background Prostate cancer (PCa) patients with elevated level of androgen receptor (AR) correlate with higher metastatic incidence. Protein expression of AR and its target gene prostate‐specific antigen (PSA) are elevated in metastatic prostate tumors as compared to organ‐confined tumors. Androgen treatment or elevation of AR promotes metastasis of PCa in cell culture and murine model. However, under androgen depleted condition, AR suppressed cell mobility and invasiveness of PCa cells. Androgen deprivation therapy in PCa patients is associated with higher risk of cancer metastasis. We therefore investigated the dual roles of AR and miRNAs on PCa metastasis. Methods The PC‐3AR (PC‐3 cells re‐expressing AR) and LNCaP cells were used as PCa cell model. Transwell migration and invasion assay, wound‐healing assay, zebrafish xenotransplantation assay, and zebrafish vascular exit assay were used to investigate the role of AR and androgen on PCa metastasis. Micro‐Western Array, co‐immunoprecipitation and Immunofluorescence were applied to dissect the molecular mechanism lying underneath. The miRNA array, miRNA inhibitors or plasmid, and chromatin immunoprecipitation assay were used to study the role of miRNAs on PCa metastasis. Results In the absence of androgen, AR repressed the migration and invasion of PCa cells. When androgen was present, AR stimulated the migration and invasion of PCa cells both in vitro and in zebrafish xenotransplantation model. Androgen increased phospho‐AR Ser81 and yes‐associated protein 1 (YAP), decreased phospho‐YAP Ser217, and altered epithelial‐mesenchymal transition (EMT) proteins in PCa cells. Co‐IP assay demonstrated that androgen augmented the interaction between YAP and AR in nucleus. Knockdown of YAP or treatment with YAP inhibitor abolished the androgen‐induced migration and invasion of PCa cells, while overexpression of YAP showed opposite effects. The miRNA array revealed that androgen decreased hsa‐miR‐5001‐5p but increased hsa‐miR‐203a and hsa‐miR‐210‐3p in PC‐3AR cells but not PC‐3 cells. Treatment with inhibitors targeting hsa‐miR‐203a/hsa‐miR‐210‐3p, or overexpression of hsa‐miR‐5001‐5p decreased YAP expression as well as suppressed the androgen‐induced migration and invasion of PCa cells. Chromatin immunoprecipitation (ChIP) assay demonstrated that AR binds with promoter region of has‐miR‐210‐3p in the presence of androgen. Conclusions Our observations indicated that miRNAs 203a/210‐3p/5001‐5p regulate the androgen/AR/YAP‐induced PCa metastasis.https://doi.org/10.1002/cam4.70106androgenARmiRNAprostate cancer metastasisYAP |
| spellingShingle | Chieh Huo Ying‐Yu Kuo Ching‐Yu Lin Shine‐Gwo Shiah Chia‐Yang Li Shu‐Pin Huang Jen‐Kun Chen Wen‐Ching Wang Hsing‐Jien Kung Chih‐Pin Chuu The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells Cancer Medicine androgen AR miRNA prostate cancer metastasis YAP |
| title | The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells |
| title_full | The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells |
| title_fullStr | The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells |
| title_full_unstemmed | The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells |
| title_short | The miRNAs 203a/210‐3p/5001‐5p regulate the androgen/androgen receptor/YAP‐induced migration in prostate cancer cells |
| title_sort | mirnas 203a 210 3p 5001 5p regulate the androgen androgen receptor yap induced migration in prostate cancer cells |
| topic | androgen AR miRNA prostate cancer metastasis YAP |
| url | https://doi.org/10.1002/cam4.70106 |
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