The SOX18-OTUB1-YAP1 axis: a new endometriosis target
Abstract Background EMS (Endometriosis) is characterized by the presence of functional endometrial tissue outside the uterus and is one of the most common gynecological disorders. SOX18 (SYR-related high-mobility group box 18) is a transcription factor whose expression is higher in ectopic endometri...
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BMC
2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06677-y |
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| author | Ying Feng Jiamei Yue Si Fan Jiayan Wu |
| author_facet | Ying Feng Jiamei Yue Si Fan Jiayan Wu |
| author_sort | Ying Feng |
| collection | DOAJ |
| description | Abstract Background EMS (Endometriosis) is characterized by the presence of functional endometrial tissue outside the uterus and is one of the most common gynecological disorders. SOX18 (SYR-related high-mobility group box 18) is a transcription factor whose expression is higher in ectopic endometrial tissues than in eutopic endometrial tissues. However, its role in EMS has not been confirmed. Methods Here, immunohistochemistry (IHC) staining was used to analyze the expression pattern of SOX18 in EMS. Next, the effects of SOX18 on cell viability, migration and invasion were investigated. Dual-luciferase reporter assay, chromatin-immunoprecipitation (ch-IP) and DNA pull-down were employed to verify SOX18 binding to the OTUB1 (OTU domain-containing ubiquitin aldehyde binding protein 1) promoter. In addition, co-immunoprecipitation (co-IP) was used to analyze the binding of OTUB1 to YAP1 (Yes-associated protein 1). Allograft mouse model of EMS was established to explore the role of SOX18 in vivo. Results In vitro results demonstrated that upregulation of SOX18 promoted the proliferation, migration and invasion of Ishikawa cells and induced the EMT process, while knockdown of SOX18 showed the opposite effect. In vivo results also confirmed that SOX18 overexpression led to the deterioration of EMS, as reflected by significant pathological changes in mice. Mechanistically, our data proved that SOX18 directly bound to the OTUB1 promoter region and activated its transcription. Further investigation demonstrated that OTUB1 deubiquitinated YAP1 and enhanced its protein stability. Rescue experiments suggested that SOX18 modulated YAP1 expression through upregulating OTUB1, indicating the role of SOX18-OTUB1-YAP1 axis in EMS. Conclusions These discoveries underscore that SOX18 contributes to the pathogenesis of EMS through promoting OTUB1 transcription and activating Hippo/YAP1 signaling pathway, which may provide a new therapeutic target for EMS. |
| format | Article |
| id | doaj-art-eeed2c985b72472688df03ed0bdbb9f0 |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-eeed2c985b72472688df03ed0bdbb9f02025-08-20T03:21:03ZengBMCJournal of Translational Medicine1479-58762025-06-0123111510.1186/s12967-025-06677-yThe SOX18-OTUB1-YAP1 axis: a new endometriosis targetYing Feng0Jiamei Yue1Si Fan2Jiayan Wu3Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang UniversityDepartment of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang UniversityAbstract Background EMS (Endometriosis) is characterized by the presence of functional endometrial tissue outside the uterus and is one of the most common gynecological disorders. SOX18 (SYR-related high-mobility group box 18) is a transcription factor whose expression is higher in ectopic endometrial tissues than in eutopic endometrial tissues. However, its role in EMS has not been confirmed. Methods Here, immunohistochemistry (IHC) staining was used to analyze the expression pattern of SOX18 in EMS. Next, the effects of SOX18 on cell viability, migration and invasion were investigated. Dual-luciferase reporter assay, chromatin-immunoprecipitation (ch-IP) and DNA pull-down were employed to verify SOX18 binding to the OTUB1 (OTU domain-containing ubiquitin aldehyde binding protein 1) promoter. In addition, co-immunoprecipitation (co-IP) was used to analyze the binding of OTUB1 to YAP1 (Yes-associated protein 1). Allograft mouse model of EMS was established to explore the role of SOX18 in vivo. Results In vitro results demonstrated that upregulation of SOX18 promoted the proliferation, migration and invasion of Ishikawa cells and induced the EMT process, while knockdown of SOX18 showed the opposite effect. In vivo results also confirmed that SOX18 overexpression led to the deterioration of EMS, as reflected by significant pathological changes in mice. Mechanistically, our data proved that SOX18 directly bound to the OTUB1 promoter region and activated its transcription. Further investigation demonstrated that OTUB1 deubiquitinated YAP1 and enhanced its protein stability. Rescue experiments suggested that SOX18 modulated YAP1 expression through upregulating OTUB1, indicating the role of SOX18-OTUB1-YAP1 axis in EMS. Conclusions These discoveries underscore that SOX18 contributes to the pathogenesis of EMS through promoting OTUB1 transcription and activating Hippo/YAP1 signaling pathway, which may provide a new therapeutic target for EMS.https://doi.org/10.1186/s12967-025-06677-yEndometriosisSOX18Hippo/YAP1OTUB1 |
| spellingShingle | Ying Feng Jiamei Yue Si Fan Jiayan Wu The SOX18-OTUB1-YAP1 axis: a new endometriosis target Journal of Translational Medicine Endometriosis SOX18 Hippo/YAP1 OTUB1 |
| title | The SOX18-OTUB1-YAP1 axis: a new endometriosis target |
| title_full | The SOX18-OTUB1-YAP1 axis: a new endometriosis target |
| title_fullStr | The SOX18-OTUB1-YAP1 axis: a new endometriosis target |
| title_full_unstemmed | The SOX18-OTUB1-YAP1 axis: a new endometriosis target |
| title_short | The SOX18-OTUB1-YAP1 axis: a new endometriosis target |
| title_sort | sox18 otub1 yap1 axis a new endometriosis target |
| topic | Endometriosis SOX18 Hippo/YAP1 OTUB1 |
| url | https://doi.org/10.1186/s12967-025-06677-y |
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