circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557

Abstract

OBJECTIVE: Accumulating evidence indicates that circular RNAs (circRNAs) contribute to breast cancer (BC) development and progression. However, the role of circ_0058063 in BC and its underlying molecular processes remain unclear. METHODS: The expression of circ_0058063, miR-557, and DLGAP5 in BC tissues and cells was determined using real time quantitative PCR or western blotting. The functions of circ_0058063 in BC cells were detected using CCK-8, Transwell, caspase-3 activity, and xenograft tumor assays. The specific binding of circ_0058063/miR-557 and DLGAP5/miR-557 was verified using RNA immunoprecipitation (RIP) and dual-luciferase reporter assays. RESULTS: circ_0058063 expression was upregulated in BC tissues and cells. circ_0058063 knockdown inhibited proliferation and migration but promoted apoptosis in MCF-7 and MDA-MB-231 cells in vitro. In vivo studies further validated that the knockdown of circ_0058063 repressed tumor growth. Mechanistically, circ_0058063 directly sponged miR-557 and negatively regulated its expression. Additionally, miR-557 inhibition reversed the tumor-suppressive effects of the circ_0058063 knockdown on the survival of MDA-MB-231 and MCF-7 cells. Moreover, miR-557 directly targeted DLGAP5. DLGAP5 knockdown suppressed MCF-7 and MDA-MB-231 cell growth, and these effects were reversed by miR-557 downregulation. CONCLUSION: Our findings verify that circ_0058063 acts as a sponge for miR-557 to upregulate DLGAP5 expression. These findings suggest that the circ_0058063/miR-557/DLGAP5 axis is an important regulator of oncogenic function and may be a promising therapeutic target for BC.