This study aimed to elucidate the molecular mechanism through which ARD1 regulates breast cancer (BC) progression via the LRRC75A-AS1/miR-489-3p axis. The expression levels of ARD1, miR-489-3p, and LRRC75A-AS1 in BC cells were quantified using reverse transcription-polymerase chain reaction (RT-PCR). The interaction between miR-489-3p and ARD1 was validated through dual-luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP). The sponge effect of LRRC75A-AS1 on miR-489-3p was confirmed by RNA pull-down assays. Functional roles of LRRC75A-AS1, miR-489-3p, and ARD1 in cell proliferation, invasion, and epithelial-to-mesenchymal transition (EMT) were evaluated using colony formation, Transwell, and western blot assays. Moreover, in vivo tumor xenograft experiments were conducted in BALB/c nude mice to assess the effect of LRRC75A-AS1 knockdown and its interaction with miR-489-3p and ARD1 on tumor growth. ARD1 promoted BC cell proliferation, invasion, and EMT. miR-489-3p was identified as a negative regulator of ARD1, while LRRC75A-AS1 acted as a competing endogenous RNA (ceRNA) that sponged miR-489-3p, thereby restoring ARD1 expression. Rescue experiments confirmed that LRRC75A-AS1 facilitated BC cell malignancy via the miR-489-3p/ARD1 axis. Importantly, in vivo studies demonstrated that silencing LRRC75A-AS1 significantly inhibited tumor growth in nude mice, accompanied by reduced ARD1 expression and increased miR-489-3p levels. The inhibitory effect on tumor growth was reversed by miR-489-3p inhibition and further restored by ARD1 knockdown, validating the functional relevance of this regulatory axis in vivo. Both in vitro and in vivo findings reveal that LRRC75A-AS1 promotes breast cancer progression by sponging miR-489-3p and upregulating ARD1. The LRRC75A-AS1/miR-489-3p/ARD1 ceRNA axis represents a novel regulatory pathway and a promising therapeutic target in BC.© 2025. The Author(s).