Circular RNA FOXO3 Suppresses Bladder Cancer Progression and Metastasis by Regulating MiR-9-5p/TGFBR2

Background: Increasing evidence indicates that the dysregulation of circular RNAs (circRNAs) plays important roles in tumor progressions. Methods: In this study, we first analyzed circ-FOXO3 level in bladder cancers (BCs), and then BC cell lines were transfected with circ-FOXO3 expression vector, and cell proliferation, migration, and invasion abilities were analyzed. We also used bioinformatics tools to predict potential-binding miRNAs for circ-FOXO3, and luciferase reporter assay was used for the verification of binding miRNAs. For the further study, we analyzed potential downstream-binding mRNA for miRNA, and cell proliferation, migration and invasion abilities of it were also studied. Results: We found that circ-FOXO3 was significantly down-regulated in bladder cancer (BC) tissues compared to normal bladder tissues. We also found that circ-FOXO3 overexpression inhibited cell proliferation, migration and invasion in BC cell lines. Moreover, we demonstrated that TGFBR2 was regulated by circ-FOXO3 through sponging miR-9-5p, the knockdown of TGFBR2 or the overexpression of miR-9-5p all related to the increased BC cell proliferation, migration, and invasion. Discussion: In summary, our data showed that circ-FOXO3 was significantly downregulated in bladder cancers. circ-FOXO3 overexpression inhibits BC cell progression and metastasis. Furthermore, circ-FOXO3 regulates TGFBR2 expression through sponging miR9-5p in BC cell lines.