Circular RNA-centered regulatory networks in breast cancer: From ceRNA crosstalk to immune microenvironment...

Circular RNAs (circRNAs) have emerged as a pervasive and functionally diverse class of regulatory molecules in breast cancer. While early studies predominantly described circRNAs as competing endogenous RNAs that modulate gene expression through microRNA sequestration, accumulating evidence indicates that this paradigm captures only a limited aspect of circRNA biology. Recent advances reveal that circRNAs function as central organizers of multilayered regulatory networks, integrating post-transcriptional control, RNA-protein interactions, noncanonical translation, metabolic adaptation, and immune microenvironment remodeling. In this review, we synthesize recent findings to propose a circRNA-centered network framework in breast cancer, highlighting how circRNAs orchestrate tumor progression, invasion, immune escape, and therapy resistance. We discuss key functional modules, including ceRNA crosstalk, RNA-binding protein scaffolding, circRNA-encoded peptides, ferroptosis and epitranscriptomic regulation, as well as immune checkpoint signaling and tumor-associated macrophage polarization. Importantly, we emphasize network-level convergence on shared signaling hubs such as PI3K/AKT, YAP/TAZ, STAT3, and cytokine-driven immune pathways, which link tumor-intrinsic plasticity to extrinsic immune suppression. Finally, we explore the translational implications of circRNA-centered networks as biomarkers and therapeutic targets, and outline future directions for integrating single-cell, spatial, and real-world clinical data. Collectively, this review reframes circRNAs from isolated regulators to central nodes of systems-level reprogramming in breast cancer, providing a conceptual foundation for network-informed precision oncology.