Khalaji Amirreza, Nazari Yousef, Pandeh Mojtaba, Farhoudian Aram, Ghorbi Leila, Naderi Pedram, Janagard Elham Mohebi, Afshari Samira Amin, Morovatshoar Reza
Student Research Committee, Tabriz University of Medical Science, Tabriz, Iran.
School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
Eur J Med Res. 2025 Aug 14;30(1):750. doi: 10.1186/s40001-025-02967-9.
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.
环状RNA（circRNAs）是乳腺癌（BC）进展中的关键调节因子，特别是通过它们与Wnt/β-连环蛋白信号通路的相互作用。这篇全面的综述阐明了关键环状RNA，包括circABCC4、circFAT1、circARL8B和circDONSON，在调节乳腺癌行为中的作用。这些环状RNA主要作为微小RNA海绵发挥作用，影响增殖、转移、耐药性和细胞存活等重要过程。例如，circDONSON通过SOX4介导的Wnt信号促进肿瘤生长和放射抗性，而circRNF10具有肿瘤抑制特性。环状RNA作为癌基因或肿瘤抑制因子的双重作用凸显了它们的复杂性。它们的高稳定性和组织特异性表达模式使其成为有前景的诊断生物标志物和治疗靶点。环状RNA的失调调节Wnt/β-连环蛋白信号通路，这是乳腺癌进展的关键驱动因素，促进肿瘤发生和治疗抗性。本综述综合了同行评审文献中的证据，强调了环状RNA与Wnt相互作用的分子机制和临床意义。通过探索这些复杂的网络，我们确定了针对乳腺癌治疗的新机会，强调了环状RNA在改变诊断和治疗方面的潜力。未来的研究应优先标准化环状RNA定量，并在不同患者队列中验证研究结果，以提高临床适用性。
