OncoTargets and Therapy (2020-01-01)

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

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

Journal volume & issue
Vol. Volume 13
pp. 931 – 944

Abstract

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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 ChinaCorrespondence: Ning WangDepartment of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110000, People’s Republic of ChinaEmail [email protected]: 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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