Abstract
Metastasis is the leading cause of breast cancer (BC)-related deaths. Circular RNAs (circRNAs) have emerged as essential regulators for cancer progression and metastasis. Therefore, the objective of this study was to investigate the role of circRNAs in BC metastasis and related mechanism. In this study, we established the BC cell line with high or low potential of metastasis. RNA sequencing, migration and invasion assay, Fluorescence in situ hybridization, luciferase report assay, circRNA pulldown, and transmission electron microscopy were performed to elucidate the molecular mechanism. The results showed that circRNA circFOXK2 was significantly increased in BC cells with high metastatic ability, and the upregulation of circFOXK2 was correlated with poor clinicopathological characteristics. Functional experiments demonstrated that overexpression of circFOXK2 promoted migration and invasion of BC cells. Also. circFOXK2 could act with IGF2BP3, an RNA-binding protein, and miR-370 to synergistically promote BC metastasis. Moreover, miR-370 could be transferred through exosomes to enhance the metastatic ability of recipient cells. In conclusion, circFOXK2 functions as a key regulator in BC metastasis, and the role of circFOXK2 on BC metastasis is tightly associated with the involvement of IGF2BP3 and miR-370. CircFOXK2 might serve as a potential biomarker for the diagnosis and treatment of BC.