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- Title
Dual roles of BK Polyomavirus in promoting urothelial carcinoma progression via regulating CLDN1.
- Authors
Xu, Cuidi; Chen, Siyue; Chen, Juntao; Wang, Jina; Niu, Xinhao; Rong, Ruiming; Zhu, Tongyu; Zeng, Yigang
- Abstract
Uncontrolled productive infection of BK polyomaviruses (BKV) in immunocompromised patients was reported to result in serious diseases, especially renourinary malignancies. However, the mechanism of BKV as a role of human carcinogen is still unknown. In this study, we showed that there is a significant association between BKV infection and metastasis of urothelial carcinoma (UCA). BKV-infected tumor tissues exhibit invasive histologic phenomena with vascular invasion and myometrial invasion. Then we identified that BKV promotes UCA invasion in a mode of dual regulation of tumor cells (TCs) invasion and endothelial cells (ECs) adhesion by encoding miRNAs. In cancer cells, BKV-B1-miR-5p promotes cell motility and invasiveness by directly targeting CLDN1. Moreover, exosomal-BKV-B1-miR-3p derived from BK-infected BC cells would be transferred to ECs and increase its adhesion to tumor cells by switching on the CLDN1 enhancer, which subsequently destroyed endothelial monolayers and increased permeability. In a human urothelial cancer metastasis mouse model, BK-inoculated cells exhibited higher incidence of vascular leakage and liver colonization. However, the vascular leakage and liver metastasis could be reduced when knocking down miRNAs in BK-inoculated cells. Our research delineates the bifunctional impact of BKV-encoded microRNAs on the expression of CLDN1 within both TCs and ECs, which orchestrates the establishment of a pre-metastatic niche in UCA.
- Subjects
TRANSITIONAL cell carcinoma; CELL adhesion; LIVER metastasis; POLYOMAVIRUSES; CELL motility; FIDDLER crabs; METASTASIS
- Publication
Biomarker Research, 2024, Vol 12, Issue 1, p1
- ISSN
2050-7771
- Publication type
Article
- DOI
10.1186/s40364-024-00564-2