AUTHOR=Luo Liping , Miao Pingping , Ming Yao , Tao Jie , Shen Hongchun TITLE=Circ-ZFR Promotes Progression of Bladder Cancer by Upregulating WNT5A Via Sponging miR-545 and miR-1270 JOURNAL=Frontiers in Oncology VOLUME=Volume 10 - 2020 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.596623 DOI=10.3389/fonc.2020.596623 ISSN=2234-943X ABSTRACT=Background: Bladder cancer is one of the most common cancers all over the world. CircZFR is a circular RNA and has been implicated in tumor generation and invasion. However, the exact role of circZFR in the development of bladder cancer (BCa) remains unknown. This study aimed to investigate the function of circZFR in BCa, and further probe into the association bwtween circ-ZFR, and two effectors, miR-545/miR-1270 and WNT5A. Methods: The expression of circZFR in BCa was quantified by qRT-PCR and was correlated with the prognosis of BCa patients. Next, the stable knockdown of circZFR BCa cell lines was established and the pertinent indicators including proliferation, migration and invasion were measured. The association of circZFR with miR-1270/miR-545 was confirmed by circinteractome prediction, luciferase assay and RNA pull down assay. The miRNA inhibitor, WNT5A overexpression and Pearson correlation analysis were used to examine the relationship among circZFR, miR-1270/miR-545 and WNT5A. Results: CircZFR was up-regulated both in BCa tissues and in BCa cell lines, and the expression level of circZFR was positively correlated with patient survival rate. Inhibiting the expression of circZFR suppressed BCa cells proliferation, migration and invasion in vitro and in vivo. Through overexpression of target miRNA, we confirmed that circZFR directly interact with miR-545 and miR-1270. Furthermore, we demonstrated that circZFR promotes progression of BCa by upregulatingWNT5A expression via sponging miR-545 and miR-1270. Conclusions: CircZFR promotes BCa cells proliferation, migration and invasion by upregulating WNT5A signaling pathway via sponging miR-1270/miR-545. These results provide new insights into the molecular mechanism of circZFR in BCa and a novel target for BCa clinical treatment.