Work

Exosomal circ_0000387 Is Associated With Ovarian Cancer Metastatic Regulation Through IGF2BP3‐Related Signalling and Endothelial VWF Responses

Year: 2026

Type: article

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.

Source: Journal of Biochemical and Molecular Toxicology

DOI: 10.1002/jbt.71135

Authors: Yulian Xie, Peijun Shen, Hailin Chen, Qianqian Shen, Xiaoxia Tong

Institutions: Fudan University, Zhongshan Hospital

Language: English

Topic: Circular RNAs in diseases

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,020