Regulatory roles of circular RNAs in Wnt and other oncogenic signaling pathways in breast cancer progression: a comprehensive review

Abstract

Circular RNAs (circRNAs) are critical regulators in breast cancer (BC) progression, particularly through their interactions with the Wnt/β-catenin signaling pathway. This comprehensive review elucidates the regulatory roles of key circRNAs, including circABCC4, circFAT1, circARL8B, and circDONSON, in modulating BC behavior. These circRNAs primarily function as microRNA sponges, influencing essential processes such as proliferation, metastasis, drug resistance, and cell survival. For instance, circDONSON promotes tumor growth and radioresistance through SOX4-mediated Wnt signaling, whereas circRNF10 exhibits tumor-suppressive properties. The dual role of circRNAs as oncogenes or tumor suppressors highlights their complexity. Their high stability and tissue-specific expression patterns position them as promising diagnostic biomarkers and therapeutic targets. Dysregulation of circRNAs modulates Wnt/β-catenin signaling, a key driver of BC progression, promoting oncogenesis and therapeutic resistance. This review synthesizes evidence from peer-reviewed literature, emphasizing the molecular mechanisms and clinical implications of circRNA-Wnt interactions. By exploring these intricate networks, we identify novel opportunities for targeted BC therapies, underscoring the potential of circRNAs to transform diagnosis and treatment. Future research should prioritize standardizing circRNA quantification and validating findings across diverse patient cohorts to enhance clinical applicability.

Keywords: Breast cancer; CircularRNAs; Molecular agents; Wnt; Wnt signaling pathway; circRNA biogenesis.

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Graphical abstract

Fig. 2

Circular RNAs as modulators of key signaling pathways in breast cancer pathogenesis. Created in BioRender. Khalaji, A. (2025) https://BioRender.com/kb2ulhy