The Dual Roles of Circular RNAs in Breast Cancer Distant Metastasis and Their Clinical Applications.

Circular RNAs (circRNAs) are emerging as crucial regulators of the progression and metastasis of breast cancer. This review examines the dual roles of circRNAs, which act as both oncogenes and tumor suppressors, in breast cancer metastasis. CircRNAs play crucial roles in processes such as the epithelial‒mesenchymal transition (EMT), angiogenesis, immune evasion, and metabolic adaptation, facilitating cancer cell invasion, survival, and colonization in distant organs such as the brain, liver, bone, and lungs. Pro-metastatic circRNAs, such as circKIF4A and circBACH1, promote metastasis by modulating signaling pathways such as the STAT3 and PI3K/AKT pathways, whereas tumor-suppressive circRNAs, including circFOXO3 and circNFIB, inhibit metastatic progression through mechanisms such as VEGF downregulation and the suppression of arachidonic acid metabolism. Although circRNAs hold promise as biomarkers and therapeutic targets, their clinical application is impeded by challenges such as targeted delivery, off-target effects, and context-dependent roles. This review highlights the current understanding of circRNA-mediated regulation of breast cancer metastasis and emphasizes future directions, including the integration of multiomics technologies and advanced delivery systems, to increase the diagnostic and therapeutic utility of circRNAs.