Circular RNAs: Emerging regulators of signaling pathways in epithelial-mesenchymal transition and angiogenesis during breast cancer progression.

Circular RNAs (circRNAs) have emerged as important regulators of gene expression and cellular activities, and abnormalities in circRNAs in breast cancer have been linked to important biological processes like epithelial-mesenchymal transition (EMT) and angiogenesis, both essential for tumor metastasis. EMT facilitates the transition of epithelial cancer cells into a mesenchymal phenotype, enhancing their invasive and migratory capabilities, while angiogenesis promotes tumor progression by forming new blood vessels. CircRNAs also interact with microRNAs to regulate signaling pathways such as TGF-β, Wnt/-catenin, and VEGF. Besides EMT and angiogenesis, studies have identified that circRNAs affect metabolic reprogramming, chemoresistance, tumor microenvironment remodeling, and immunological evasion. Thus, circRNAs play a multifaceted role in the development of breast cancer. They hold potential as non-invasive biomarkers and therapeutic targets due to their high stability, resistance to exonuclease degradation, abundance in body fluids, and diverse expression patterns across different tissues. This review summarizes and critically assesses existing understanding of the functional roles and molecular processes of circRNAs in controlling EMT and angiogenesis during breast cancer progression.