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Circular RNA Circ_0025033 Promotes the Evolvement of Ovarian Cancer Through the Regulation of miR-330-5p/KLK4 Axis

Authors Cheng H, Wang N, Tian J, Li Y, Ren L, Shi Z

Received 6 December 2019

Accepted for publication 31 March 2020

Published 23 April 2020 Volume 2020:12 Pages 2753—2765

DOI https://doi.org/10.2147/CMAR.S241372

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Hailing Cheng,1,* Ning Wang,1,* Jun Tian,1 Yanyun Li,1 Lu Ren,1 Zhenyu Shi2

1Department of Obstetrics and Gynecology, Huaihe Hospital of Henan University, Kaifeng, Henan, People’s Republic of China; 2Henan Medical School, Henan University, Kaifeng, Henan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhenyu Shi
Henan Medical School, Henan University, Section 229, North of Jinming Avenue, Kaifeng City, Henan Province, People’s Republic of China
Tel +86-371-22922953
Email xzmkra@163.com

Background: Circular RNAs (circRNAs) are significant molecular targets in various types of human cancers. The functional mechanism of circRNA_0025033 (circ_0025033) in ovarian cancer (OC) was discussed in the current report.
Methods: The quantitative real-time polymerase chain reaction (qRT-PCR) was used for determining the circ_0025033 and microRNA-330-5p (miR-330-5p) levels. Cell Counting Kit-8 (CCK-8) and transwell assays were separately exploited to analyze cell viability and migration/invasion. Cell apoptosis was assessed using flow cytometry. The protein levels of epithelial–mesenchymal transition (EMT)-related makers and kallikrein-related peptidase 4 (KLK4) were measured by Western blotting. The target combination was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and RNA pull-down assays. And the effect of circ_0025033 on OC in vivo was explored via xenograft tumor assay.
Results: Circ_0025033 was overexpressed in OC tissues and cells. Circ_0025033 knockdown inhibited OC cell viability, migration, invasion and EMT while expedited apoptosis. MiR-330-5p was a target of circ_0025033 and circ_0025033 regulated OC cellular behaviors by sequestering miR-330-5p. Moreover, miR-330-5p targeted KLK4 and circ_0025033 affected the KLK4 expression by sponging miR-330-5p. And miR-330-5p functioned as a tumor inhibitor in OC via targeting KLK4. In vivo, circ_0025033 promoted OC growth by the miR-330-5p/KLK4 axis.
Conclusion: This study demonstrated that circ_0025033 contributed to the progression of OC via the miR-330-5p/KLK4 axis and might be a candidate target in the identification and treatment of OC.

Keywords: circ_0025033, ovarian cancer, miR-330-5p, KLK4

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