Open Access

ARTICLE

miR-146a Inhibits Proliferation and Enhances Chemosensitivity in Epithelial Ovarian Cancer via Reduction of SOD2

YaJie Cui^*†, Kai’e She^‡, Defu Tian^§, Peilian Zhang^†, Xiaoyan Xin^*

* Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
† Department of Obstetrics and Gynecology, Xi’an No. 1 Hospital, Xi’an, China
‡ Department of Obstetrics and Gynecology, Shaanxi Provincial People’s Hospital, Xi’an, China
§ Department of General Surgery, Shaanxi Provincial Fourth People’s Hospital, Xi’an, China

Oncology Research 2015, 23(6), 275-282. https://doi.org/10.3727/096504016X14562725373798

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, accounting for 90% of all ovarian cancer. Dysregulation of miRNAs is associated with several types of EOC. In the current research, we aimed to study the role of abnormal expression of miR-146a in the development of EOC and to elucidate the possible molecular mechanisms. Compared with control samples, mRNA expression of miR-146a was significantly decreased in EOC tissues and cell lines. Overexpression of miR-146a prohibited cell proliferation, enhanced apoptosis, and increased sensitivity to chemotherapy drugs in EOC cells. In contrast, downregulation of miR-146a promoted cell proliferation, suppressed apoptosis, and decreased sensitivity to chemotherapy drugs in EOC cells. Overexpression of miR-146a increased the reactive oxygen species (ROS) level and decreased SOD2 mRNA and protein expression. Downregulation of miR-146a increased SOD2 mRNA and protein expression. Overexpression of SOD2 significantly inhibited miR-146a mimicsinduced suppression of cell proliferation and the increase of apoptosis and chemosensitivity. In conclusion, we identify miR-146a as a potential tumor suppressor in patients with EOC. miR-146a downregulates the expression of SOD2 and enhances ROS generation, leading to increased apoptosis, inhibition of proliferation, and enhanced sensitivity to chemotherapy. The data demonstrate that the miR-146a/SOD2/ROS pathway may serve as a novel therapeutic target and prognostic marker in patients with EOC.

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