Circular RNA circ_0000518 promotes breast cancer progression through the microRNA-1225-3p/SRY-box transcription factor 4 pathway

This work is designed to probe the functions and mechanisms of circ_0000518 in breast cancer (BC). qRT-PCR was performed to evaluate the circ_0000518, miR-1225-3p and Sry‑Related HMG box 4 (SOX4) mRNA expression in BC tissues and cells. After circ_0000518 was overexpressed in MDA-MB-468 cells, and circ_0000518 was knocked down in BT549 cells, CCK-8 test, and EdU assay were performed to measure the viability and growth of MDA-MB-468 and BT549 cells. Wound healing experiment was executed to determine the migration of BC cells. The invasion of cells was studied by the Transwell assay. Bioinformatics analysis, dual-luciferase reporter gene assay, qRT-PCR and Western blot were applied to predict and verify the binding sites between circ_0000518 and miR-1225-3p, miR-1225-3p and SOX4 mRNA. Pearson's correlation analysis was utilized to evaluate the correlations among circ_0000518 expression, miR-1225-3p expression, and SOX4 mRNA expression in BC specimens. It was revealed that, circ_0000518 and SOX4 mRNA expression levels were up-modulated in BC tissues, while miR-1225-3p expression was down-modulated in BC tissues than that in adjacent tissues. Circ_0000518 overexpression or inhibition of miR-1225-3p remarkably enhanced the growth, migration as well as invasion of BC cells in vitro, whereas circ_0000518 knockdown or miR-1225-3p overexpression worked oppositely. Circ_0000518 was identified as a molecular sponge of miR-1225-3p, and it can up-regulate SOX4 mRNA expression via repressing miR-1225-3p. In conclusion, circ_0000518 is oncogenic in BC and functions through miR-1225-3p/SOX4 axis.