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

Authors Li Y, Qiao L, Zang Y, Ni W, Xu Z

Received 30 March 2020

Accepted for publication 5 June 2020

Published 25 June 2020 Volume 2020:12 Pages 5049—5056

DOI https://doi.org/10.2147/CMAR.S253412

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Harikrishna Nakshatri


Yongxiang Li,1,2 Liang Qiao,2 Yuanwei Zang,1 Wenjun Ni,3 Zhonghua Xu1

1Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Department of Urology, Weifang People’s Hospital, Weifang 261000, People’s Republic of China; 3Department of Urology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China

Correspondence: Zhonghua Xu
Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China
Tel +86-531-82166701
Fax +86-531-86927544
Email bildsc@163.com

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 down-regulated in bladder cancers. circ-FOXO3 overexpression inhibits BC cell progression and metastasis. Furthermore, circ-FOXO3 regulates TGFBR2 expression through sponging miR-9-5p in BC cell lines.

Keywords: bladder cancer, circ-FOXO3, miR-9-5p, TGFBR2

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