Exosomal circ_0000387 Is Associated With Ovarian Cancer Metastatic Regulation Through IGF2BP3‐Related Signalling and Endothelial VWF Responses
- 1Department of Gynaecology Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University Shanghai China
- 2Department of Gynaecology Luodian Hospital Shanghai China
Abstract
This study investigated the context‐dependent roles of circ_0000387 in ovarian cancer (OC) metastasis, focusing on its tumour‐cell‐intrinsic effects and exosome‐mediated tumour–endothelial communication. circRNA sequencing was performed on paired primary and metastatic ovarian cancer tissues to identify metastasis‐associated circRNAs. Gain‐ and loss‐of‐function experiments in SKOV3 cells assessed malignant phenotypes, while CHIRP and RIP assays examined the interaction between circ_0000387 and IGF2BP3. Exosomes were isolated and characterised, and SKOV3–endothelial cell co‐culture experiments evaluated exosome‐associated effects on endothelial VWF responses and tumour‐cell behaviour. An intraperitoneal dissemination mouse model was used for in vivo validation. circ_0000387 was expressed at higher levels in metastatic ovarian cancer tissues than in paired primary tumours. In SKOV3 cells, circ_0000387 interacted with IGF2BP3 and promoted cell viability, invasion, and migration, accompanied by AKT activation, AMPK inhibition, and increased YAP nuclear accumulation. In contrast, circ_0000387‐enriched exosomes increased endothelial VWF secretion and were associated with reduced SKOV3 invasion and migration in an FVIII‐modulated co‐culture context, accompanied by increased AMPK activation and reduced YAP nuclear accumulation. These effects were attenuated by inhibition of exosome release or VWF blockade. In vivo, circ_0000387 overexpression was associated with reduced intraperitoneal dissemination and ascites formation, and these effects were attenuated by Rab27a silencing or VWF neutralisation. circ_0000387 exhibits context‐dependent functions in ovarian cancer, promoting malignant phenotypes within tumour cells through IGF2BP3‐associated AKT/AMPK/YAP signalling while being associated with reduced metastatic activity through exosome‐dependent, VWF‐related tumour–endothelial responses. These findings identify circ_0000387 as a potential regulator of ovarian cancer metastasis warranting further mechanistic and clinical validation.
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BibTeX
@article{xie2026exosomal,
title = {{Exosomal circ_0000387 Is Associated With Ovarian Cancer Metastatic Regulation Through IGF2BP3‐Related Signalling and Endothelial VWF Responses}},
author = {Yulian Xie and Peijun Shen and Hailin Chen and Qianqian Shen and Xiaoxia Tong},
journal = {Journal of Biochemical and Molecular Toxicology},
year = {2026},
month = nov,
doi = {10.1002/jbt.71135},
url = {https://doi.org/10.1002/jbt.71135},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exosomal circ_0000387 Is Associated With Ovarian Cancer Metastatic Regulation Through IGF2BP3‐Related Signalling and Endothelial VWF Responses
AU - Yulian Xie
AU - Peijun Shen
AU - Hailin Chen
AU - Qianqian Shen
AU - Xiaoxia Tong
PY - 2026
DA - 2026/11/04
JO - Journal of Biochemical and Molecular Toxicology
DO - 10.1002/jbt.71135
UR - https://doi.org/10.1002/jbt.71135
AB - This study investigated the context‐dependent roles of circ_0000387 in ovarian cancer (OC) metastasis, focusing on its tumour‐cell‐intrinsic effects and exosome‐mediated tumour–endothelial communication. circRNA sequencing was performed on paired primary and metastatic ovarian cancer tissues to identify metastasis‐associated circRNAs. Gain‐ and loss‐of‐function experiments in SKOV3 cells assessed malignant phenotypes, while CHIRP and RIP assays examined the interaction between circ_0000387 and IGF2BP3. Exosomes were isolated and characterised, and SKOV3–endothelial cell co‐culture experiments evaluated exosome‐associated effects on endothelial VWF responses and tumour‐cell behaviour. An intraperitoneal dissemination mouse model was used for in vivo validation. circ_0000387 was expressed at higher levels in metastatic ovarian cancer tissues than in paired primary tumours. In SKOV3 cells, circ_0000387 interacted with IGF2BP3 and promoted cell viability, invasion, and migration, accompanied by AKT activation, AMPK inhibition, and increased YAP nuclear accumulation. In contrast, circ_0000387‐enriched exosomes increased endothelial VWF secretion and were associated with reduced SKOV3 invasion and migration in an FVIII‐modulated co‐culture context, accompanied by increased AMPK activation and reduced YAP nuclear accumulation. These effects were attenuated by inhibition of exosome release or VWF blockade. In vivo, circ_0000387 overexpression was associated with reduced intraperitoneal dissemination and ascites formation, and these effects were attenuated by Rab27a silencing or VWF neutralisation. circ_0000387 exhibits context‐dependent functions in ovarian cancer, promoting malignant phenotypes within tumour cells through IGF2BP3‐associated AKT/AMPK/YAP signalling while being associated with reduced metastatic activity through exosome‐dependent, VWF‐related tumour–endothelial responses. These findings identify circ_0000387 as a potential regulator of ovarian cancer metastasis warranting further mechanistic and clinical validation.
SN - 1095-6670
SN - 1099-0461
ER -