Advances in the roles and molecular mechanisms of exosomal circular RNAs in regulating the pre-metastatic niche of tumors

Metastasis remains a major cause of morbidity and mortality in patients with malignant tumors. The pre-metastatic niche is a prerequisite for distant metastasis driven by primary tumors. Circular RNAs (circRNAs), a class of single-stranded closed non-coding RNAs, exhibit high stability, evolutionary conservation, and cell-type specificity. Exosomes, as natural carriers of circRNAs, mediate intercellular communication and contribute to the formation of the pre-metastatic niche; however, the mechanisms by which they do so remain incompletely understood. This review summarizes the biological characteristics and functions of exosomal circRNAs and outlines the molecular pathways through which they shape the tumor pre-metastatic microenvironment, with emphasis on immunosuppression, vascular permeability, extracellular matrix remodeling, and lymphangiogenesis. This is the first review to focus on the functional roles and molecular mechanisms of exosomal circRNAs in pre-metastatic niche regulation, providing a basis for the development of therapeutic strategies targeting metastatic progression.