Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition
Abstract The peritoneum is the most common site of metastasis in advanced gastric cancer (GC), and the mechanisms underlying this process of gastric cancer peritoneal metastasis (GCPM) remain largely elusive. Mesothelial-mesenchymal transition (MMT) plays a crucial role in the progression of GCPM. I...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-06-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07749-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850100501530542080 |
|---|---|
| author | Chao Dong Yajing Zhou Xiaochun Shen Shuo Hu Kaipeng Duan Tao Chen Weikang Li Xiaotong Sun Peiyuan Li Pengbo Wang Ye Han Dongbao Li Qiaoming Zhi Jin Zhou |
| author_facet | Chao Dong Yajing Zhou Xiaochun Shen Shuo Hu Kaipeng Duan Tao Chen Weikang Li Xiaotong Sun Peiyuan Li Pengbo Wang Ye Han Dongbao Li Qiaoming Zhi Jin Zhou |
| author_sort | Chao Dong |
| collection | DOAJ |
| description | Abstract The peritoneum is the most common site of metastasis in advanced gastric cancer (GC), and the mechanisms underlying this process of gastric cancer peritoneal metastasis (GCPM) remain largely elusive. Mesothelial-mesenchymal transition (MMT) plays a crucial role in the progression of GCPM. In our current study, the data confirmed that GC-derived exosomes could significantly promote peritoneal metastasis through an MMT-dependent manner in vivo and in vitro. Using RNA-seq, we successfully identified a key circular RNA (circPTBP3). The expression of exosomal circPTBP3 in the plasma of GCPM patients was significantly upregulated and closely correlated with tumor differentiation, depth of invasion, lymphatic invasion, peritoneal metastasis, and TNM stage. Exosomal circPTBP3 thus serves as a reliable diagnostic and prognostic indicator in GCPM patients. Mechanistically, exosomal circPTBP3 could effectively promote the MMT phenotype of mesothelial cells in vitro. Located in the nucleus, circPTPB3 was found to recruit transcription factor AP-2-beta (TFAP2B) to the serum- and glucocorticoid-inducible kinase 1 (SGK1) promoter sites, thereby initiating its transcription in mesothelial cells. These findings suggest that exosomal circPTPB3 functions as a pivotal mediator in facilitating the interplay between GC cells and mesothelial cells, and it provides a promising diagnostic indicator and therapeutic target for GCPM patients. |
| format | Article |
| id | doaj-art-1af368339ddd46fda31465cd66903848 |
| institution | DOAJ |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-1af368339ddd46fda31465cd669038482025-08-20T02:40:17ZengNature Publishing GroupCell Death and Disease2041-48892025-06-0116111710.1038/s41419-025-07749-zTumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transitionChao Dong0Yajing Zhou1Xiaochun Shen2Shuo Hu3Kaipeng Duan4Tao Chen5Weikang Li6Xiaotong Sun7Peiyuan Li8Pengbo Wang9Ye Han10Dongbao Li11Qiaoming Zhi12Jin Zhou13Department of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityDepartment of General Surgery, The First Affiliated Hospital of Soochow UniversityAbstract The peritoneum is the most common site of metastasis in advanced gastric cancer (GC), and the mechanisms underlying this process of gastric cancer peritoneal metastasis (GCPM) remain largely elusive. Mesothelial-mesenchymal transition (MMT) plays a crucial role in the progression of GCPM. In our current study, the data confirmed that GC-derived exosomes could significantly promote peritoneal metastasis through an MMT-dependent manner in vivo and in vitro. Using RNA-seq, we successfully identified a key circular RNA (circPTBP3). The expression of exosomal circPTBP3 in the plasma of GCPM patients was significantly upregulated and closely correlated with tumor differentiation, depth of invasion, lymphatic invasion, peritoneal metastasis, and TNM stage. Exosomal circPTBP3 thus serves as a reliable diagnostic and prognostic indicator in GCPM patients. Mechanistically, exosomal circPTBP3 could effectively promote the MMT phenotype of mesothelial cells in vitro. Located in the nucleus, circPTPB3 was found to recruit transcription factor AP-2-beta (TFAP2B) to the serum- and glucocorticoid-inducible kinase 1 (SGK1) promoter sites, thereby initiating its transcription in mesothelial cells. These findings suggest that exosomal circPTPB3 functions as a pivotal mediator in facilitating the interplay between GC cells and mesothelial cells, and it provides a promising diagnostic indicator and therapeutic target for GCPM patients.https://doi.org/10.1038/s41419-025-07749-z |
| spellingShingle | Chao Dong Yajing Zhou Xiaochun Shen Shuo Hu Kaipeng Duan Tao Chen Weikang Li Xiaotong Sun Peiyuan Li Pengbo Wang Ye Han Dongbao Li Qiaoming Zhi Jin Zhou Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition Cell Death and Disease |
| title | Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition |
| title_full | Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition |
| title_fullStr | Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition |
| title_full_unstemmed | Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition |
| title_short | Tumor exosomal circPTBP3 drives gastric cancer peritoneal metastasis via mesothelial-mesenchymal transition |
| title_sort | tumor exosomal circptbp3 drives gastric cancer peritoneal metastasis via mesothelial mesenchymal transition |
| url | https://doi.org/10.1038/s41419-025-07749-z |
| work_keys_str_mv | AT chaodong tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT yajingzhou tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT xiaochunshen tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT shuohu tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT kaipengduan tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT taochen tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT weikangli tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT xiaotongsun tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT peiyuanli tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT pengbowang tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT yehan tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT dongbaoli tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT qiaomingzhi tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition AT jinzhou tumorexosomalcircptbp3drivesgastriccancerperitonealmetastasisviamesothelialmesenchymaltransition |