Mehran Molavand
1,2* 
, Maryam Majidinia
3 , Bahman Yousefi
1* 1 Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
3 Solid Tumor Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
Abstract
Breast cancer, a complex and heterogeneous disease marked by uncontrolled cell growth in breast tissue, presents a significant global health challenge due to its high mortality rate. Metastasis, a major driver of cancer progression and mortality, poses a significant challenge in clinical oncology. This complex process involves profound changes in cytoskeletal dynamics and interactions with the extracellular matrix, including integrin-mediated adhesion and the activity of matrix metalloproteinases (MMPs). Circular RNAs (circRNAs) are a type of endogenous non-coding RNA with a covalently closed-loop structure. They serve as critical regulators of gene expression and modulate essential cellular processes, including proliferation, cell cycle control, and invasion. Through intricate interactions with key signaling pathways, including Wnt/β-catenin, PI3K/AKT, TGF-β/SMAD, and the MEK-MAPK pathway, circRNAs modulate these processes, particularly epithelial-to-mesenchymal transition (EMT), which is crucial in breast cancer metastasis. Mechanistically, circRNAs activate transcription factors associated with EMT, such as Slug, Snail, Twist, and Zeb. Moreover, circRNAs have emerged as promising clinical biomarkers in breast cancer, offering new opportunities for early diagnosis, prognostic assessment, and the development of targeted therapeutic strategies. In this article, the role of circRNAs in modulating EMT-regulating signaling pathways in the context of breast cancer metastasis will be reviewed.