Tumour-derived exosomal piR-25783 promotes omental metastasis of ovarian carcinoma by inducing the fibroblast to myofibroblast transition

Ovarian carcinoma inherently possesses a distinct metastatic organotropism for the adipose-rich omentum, contributing to disease progression. Although the premetastatic microenvironment (PMM) has been known to often play a prometastatic role during the process, incomplete mechanistic insight into PMM formation has prevented its therapeutic targeting. Omental fibroblasts can be activated by tumour cells to differentiate into myofibroblasts, termed the fibroblast-to-myofibroblast transition (FMT), which, in turn, enhances cancer aggressiveness. Here, we report crosstalk between cancer cells and omental fibroblasts through exosomal piR-25783, which fuels tumour metastasis. Tumour cell-secreted exosomal piR-25783 activates the TGF-β/SMAD2/SMAD3 pathway in fibroblasts and promotes the FMT in the omentum along with the secretion of various cytokines and elevation of proliferative, migratory, and invasive properties, contributing to the formation of PMMs. Furthermore, piR-25783-induced myofibroblasts promote tumour implantation and growth in the omentum. In addition, the overexpression of piR-25783 in ovarian carcinoma is associated with unfavourable clinicopathological characteristics and shorter survival. In this study, we provide molecular, functional, and translational evidence suggesting that exosomal piR-25783 plays an important role in the formation of PMMs and the development of metastatic diseases in vitro and in vivo and may serve as a potential therapeutic target for ovarian carcinoma with metastasis. This is a preview of subscription content, access via your institution Access options Subscribe to this journal Receive 50 print issues and online access 251,40 € per year only 5,03 € per issue Buy this article - Purchase on SpringerLink - Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout Similar content being viewed by others Data availability The datasets generated and/or analysed during the current study are available from the corresponding author upon reasonable request.

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This work was supported by the National Natural Science Foundation of China (Nos. 81772781, 81903012, 81902665). The authors acknowledge the use of Biorender that is used to create Graphical Abstract. Author information Authors and Affiliations Contributions ZW and LX conceived the project. GL and XY conducted most of the experimental work and wrote the manuscript. SD and LG performed the animal experiments. SS and LC collected the clinical samples. QW and YC analysed the clinical data. JC supervised the project. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Competing interests The authors declare no competing interests. Ethical approval All procedures involving human specimens were approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (Wuhan, China). Written informed consent was obtained from all patients. All experimental procedures used in the animal studies were approved by the Tongji Medical College’s Animal Care and Use Committee, Huazhong University of Science and Technology. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Li, G., Yi, X., Du, S. et al. Tumour-derived exosomal piR-25783 promotes omental metastasis of ovarian carcinoma by inducing the fibroblast to myofibroblast transition. Oncogene 42, 421–433 (2023). https://doi.org/10.1038/s41388-022-02560-y Received: Revised: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1038/s41388-022-02560-y