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MiR-195-5p Inhibits Malignant Progression of Cervical Cancer by Targeting YAP1

Authors Liu X, Zhou Y, Ning Y, Gu H, Tong Y, Wang N

Received 19 August 2019

Accepted for publication 20 January 2020

Published 30 January 2020 Volume 2020:13 Pages 931—944

DOI https://doi.org/10.2147/OTT.S227826

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sanjay Singh


Xiaomin Liu,1 Yi Zhou,1 Yu-e Ning,1 Hui Gu,2 Yuxin Tong,3 Ning Wang1

1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110000, People’s Republic of China; 2Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang 110004, People’s Republic of China; 3Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, People’s Republic of China

Correspondence: Ning Wang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110000, People’s Republic of China
Email nonaware@sina.com

Purpose: Our previous studies have shown that miR-195 is reduced in cervical cancer tissues, and that upregulation of miR-195 suppressed cervical cancer cell growth and induced a cell cycle block. In this study, we aimed to further elucidate the mechanism of action between miR-195-5p and Yes-associated protein 1 (YAP1) in the malignant progression of cervical cancer.
Methods: MiR-195-5p and YAP1 were detected using qRT-PCR in cervical cancer cells transfected with miR-195-5p mimics or inhibitor. Cell proliferation, migration, and invasion ability were detected using MTT, wound healing, and transwell invasion assays. Dual luciferase reporter assay, qRT-PCR, and Western blot analysis were used to demonstrate that YAP1 was a target of miR-195-5p.
Results: Our results showed that miR-195-5p is negatively correlated with YAP1 protein levels but not with mRNA expression. Moreover, upregulation of miR-195-5p by transient transfection with miR-195-5p mimics in HeLa and SiHa cells inhibited cell proliferation, migration ability, invasiveness, and the EMT. Conversely, miR-195-5p downregulation produced opposite results. In addition, multiple miRNA target prediction sites showed that YAP1 was a potential target gene; this was confirmed by dual luciferase assay. Rescue experiments further confirmed that YAP1 is involved in miR-195-5p-mediated inhibition of proliferation, migration ability, invasiveness, and the EMT of cervical cancer cells.
Conclusion: Taken together, our data suggest that miR-195-5p may act as a tumor suppressor which could provide a theoretical basis for cervical cancer patient targeted therapy.

Keywords: cervical cancer, miR-195-5p, YAP1, epithelial to mesenchymal transition

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