In our study, we demonstrated that (i) miR-21 regulated miR-34b/c through affecting PI3K/AKT/FOXO3a signaling; (ii) circulating miR-21 and miR-34b/c have clinical implication for providing novel biomarkers for BC diagnosis; and (iii) targeting miR-21and/or restoring miR-34b/c may possess therapeutic applications for BC treatment in the future. This evidence concerns the gene FOXO3 and breast cancer.