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miR-204 Negatively Regulates Cell Growth And Metastasis By Targeting ROBO4 In Human Bladder Cancer

Authors Li Y, Chen R, Li Z, Cheng H, Li X, Li T, Zhu C

Received 12 February 2019

Accepted for publication 20 September 2019

Published 16 October 2019 Volume 2019:12 Pages 8515—8524

DOI https://doi.org/10.2147/OTT.S205023

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Rachel Predeepa

Peer reviewer comments 2

Editor who approved publication: Dr Takuya Aoki


Yang Li,1,* Rong Chen,2,* Zun Li,1 Hepeng Cheng,1 Xiaodong Li,1 Tieqiang Li,1 Chaoyang Zhu1

1Department of Urology, Henan University Huaihe Hospital, Kaifeng 475000, People’s Republic of China; 2Department of Urology, Zhuji People’s Hospital of Zhejiang Province, Zhuji 311800, China

*These authors contributed equally to this work

Correspondence: Chaoyang Zhu
Department of Urology, Henan University Huaihe Hospital, No. 8 Baobei Road, Kaifeng, Henan Province 475000, People’s Republic of China
Email chaoyangz_hn@163.com

Background: MicroRNAs (miRNAs) are well characterized for their important roles in human cancers by influencing various aspects of malignancy. Till now, the function and mechanism of miR-204, a tumor suppressor in several cancers, remain unclear in bladder cancer (BC). Here, we intend to explore its roles in BC progression.
Methods: qRT-PCR was applied to determine miR-204 and ROBO4 expression in BC tissues and cell lines. miR-204 expression with clinicopathological features was analyzed. The impacts of miR-204 on BC cell growth and metastasis in vitro were evaluated by both loss-of-function and gain-of-function assays (CCK-8, crystal violet staining, wound healing and transwell assays). Furthermore, qRT-PCR, Western blot and luciferase reporter assays were used to validate the targeting of ROBO4 by miR-204. Finally, linear regression was performed to analyze the correlation of miR-204 and ROBO4 in BC tissues.
Results: Expression of miR-204 was markedly decreased in BC tissues and cell lines were compared with respective controls. Low miR-204 expression was associated with positive advanced T stage and lymph node metastasis. Cellular function studies revealed that miR-204 inhibited BC cell growth, migration and invasion. Mechanistic exploration found that miR-204 directly targeted ROBO4. Rescue assays indicated that ROBO4 restoration could reverse the antitumor effects of miR-204 in BC. Finally, ROBO4 was significantly correlated with miR-204 levels inversely.
Conclusion: miR-204 might serve as a tumor suppressor in BC by targeting ROBO4.

Keywords: BC, miR-204, ROBO4, cell growth and metastasis

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