MicroRNA‑138 inhibits tumor growth and enhances chemosensitivity in human cervical cancer by targeting H2AX

Yuan,Min; Zhao,Shuting; Chen,Rui; Wang,Guozeng; Bie,Yachun; Wu,Qianyu; Cheng,Jingxin

doi:10.3892/etm.2019.8238

MicroRNA‑138 inhibits tumor growth and enhances chemosensitivity in human cervical cancer by targeting H2AX

Authors:
- Min Yuan
- Shuting Zhao
- Rui Chen
- Guozeng Wang
- Yachun Bie
- Qianyu Wu
- Jingxin Cheng
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Affiliations: Department of Gynecology, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Department of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, Pudong New Area, Shanghai 200120, P.R. China
Published online on: November 22, 2019 https://doi.org/10.3892/etm.2019.8238
Pages: 630-638
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNA‑138 (miR‑138) acts as a key regulator in the modulation of carcinogenesis in numerous tumor types. Chemoresistance is common and relevant to the failure of multiple treatment strategies for cervical cancer. However, the biological role of miR‑138 in the progression and chemosensitivity of cervical cancer is still unclear. The present study aimed to investigate the expression, function and mechanism of miR‑138 in cervical cancer. An miR‑138 mimic, inhibitor and negative control were transfected into SiHa and C33A cells. The expression of miR‑138 and its target were assessed by reverse transcription‑PCR, western blotting and immunohistochemistry. The functional significance of miR‑138 in tumor progression and chemosensitivity to cisplatin in vitro was examined by Cell Counting Kit‑8, flow cytometry, wound healing and Transwell assays. A tumor xenograft model was used to validate the effects in vivo. These results demonstrated that miR‑138 was significantly downregulated in cervical cancer cells. Overexpression of miR‑138 suppressed cervical cancer cell proliferation, invasion, increased apoptosis and enhanced chemotherapy sensitivity in vivo and in vitro. Furthermore, bioinformatics analysis and dual luciferase reporter assays demonstrated that H2AX served as a target for miR‑138, and the rescue experiment revealed that H2AX was a functional target of miR‑138. The protective effects of miR‑138 overexpression were dependent on H2AX. This study provides evidence that miR‑138/H2AX may be a novel therapeutic target in cervical cancer.

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