Abstract
BACKGROUND: As a frequently occurring malignant disorder in women, breast cancer (BC) is closely associated with circular RNAs (circRNAs) in mediating its pathological progression. Accumulating evidence suggests that hsa_circ_0001588 promotes BC via microRNA (miRNA) sponging. AIM: To investigate the expression dynamics, functional contributions, and molecular underpinnings of hsa_circ_0001588 in BC progression, focusing on its regulatory axis with miR-525-3p and KPNB1. METHODS: Clinical BC tissues and cell lines were used to validate hsa_circ_0001588 expression via RT-qPCR. Cell proliferation was evaluated via MTT assay, whereas migration and invasion capacities were assessed using Transwell systems. Dual-luciferase reporter assays and RIP were implemented to validate the reciprocal interactions among hsa_circ_0001588, miR-525-3p, and KPNB1. Rescue strategies involving miR-525-3p inhibition or KPNB1 overexpression were thereafter executed to validate the regulatory axis. RESULTS: Hsa_circ_0001588 exhibited elevated expression in BC tissues and cell lines, demonstrating positive associations with advanced TNM staging and unfavorable prognosis. Depletion of hsa_circ_0001588 impaired proliferative, migratory, and invasive capacities, as well as EMT in cells. Mechanistically, hsa_circ_0001588 directly binds to miR-525-3p, relieving its repression on KPNB1. The inhibitory effects resulting from the knockdown of hsa_circ_0001588 can be reversed by either inhibiting miR-525-3p or overexpressing KPNB1. CONCLUSIONS: Hsa_circ_0001588 emerges as a critical regulator of BC malignancy by modulating the miR-525-3p/KPNB1 axis. Its overexpression correlates with poor prognosis, positioning it as a promising diagnostic marker and actionable therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-00920-0.