Tabriz University of Medical Sciences BioImpacts 2228-5652 16 1 2026 01 04 The involvement of circular RNAs in breast cancer metastasis: Insight into EMT-related signaling pathways 32903 32903 10.34172/bi.32903 EN Mehran Molavand https://orcid.org/0009-0007-3923-7549 Maryam Majidinia https://orcid.org/0000-0001-9776-5816 Bahman Yousefi https://orcid.org/0000-0002-4220-1527 Journal Article 10.34172/bi.32903 2025 10 05 2025 12 30 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.