miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

Cui,Yajie; Wu,Fengqin; Tian,Defu; Wang,Ting; Lu,Tianjie; Huang,Xiying; Zhang,Peilian; Qin,Li

doi:10.3892/or.2018.6259

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

Authors:
- Yajie Cui
- Fengqin Wu
- Defu Tian
- Ting Wang
- Tianjie Lu
- Xiying Huang
- Peilian Zhang
- Li Qin
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Affiliations: Department of Obstetrics and Gynecology, Xi'an No. 4 Hospital, Xi'an, Shaanxi 710002, P.R. China, Department of Gynecology, Shangluo Central Hospital, Shangluo, Shaanxi 726000, P.R. China, Department of General Surgery, Shaanxi Provincial Fourth People's Hospital, Xi'an, Shaanxi 710006, P.R. China, Reproductive Medicine Center, Northwest Women and Children's Hospital, Xi'an, Shaanxi 710061, P.R. China, Department of Obstetrics and Gynecology, Xi'an No. 1 Hospital, Xi'an, Shaanxi 710002, P.R. China, Department of Obstetrics and Gynecology, Shaanxi Province People's Hospital, Xi'an, Shaanxi 710033, P.R. China
Published online on: February 12, 2018 https://doi.org/10.3892/or.2018.6259
Pages: 1649-1657
Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Drug resistance remains a large obstacle for the treatment of ovarian cancer. miRNAs have been reported to be involved in cisplatin (CDDP) resistance in ovarian cancer. The aim of the present study was to investigate the function and mechanism of miR-199a-3p in the CDDP resistance in ovarian cancer. We found that miR-199a-3p was significantly downregulated in chemoresistant ovarian cancer tissues, as well as CDDP-resistant SKOV3/CDDP cells, compared to chemosensitive carcinomas and SKOV3 cells. Restoration of miR-199a-3p in SKOV3/CDDP cells reduced cell proliferation, G1 phase cell cycle arrest, cell invasion, and increased cell apoptosis, resulting in enhanced CDDP sensitivity, while miR-199a-3p inhibition resulted in the opposite effects. Luciferase reporter assay showed that integrin β8 (ITGB8), one of the integrins that is involved in the regulation of cell cycle and motility, was a direct target of miR-199a-3p. Overexpression of miR-199a-3p downregulated ITGB8 expression via binding to its 3'-UTR. In addition, overexpression of ITGB8 restored CDDP resistance inhibited by miR-199a-3p. Moreover, orthotopic ovarian cancer mouse model showed that miR‑199a-3p enhanced CDDP sensitivity of ovarian cancer in vivo. Therefore, our results indicate that miR-199a-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ITGB8 expression, and miR-199a-3p may serve as a therapeutic target for the treatment of ovarian cancer patients with CDDP-resistance.

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