miR-146b promotes cell proliferation and increases chemosensitivity, but attenuates cell migration and invasion via FBXL10 in ovarian cancer

miR-146b 促进细胞增殖并增加化学敏感性,但通过 FBXL10 减弱卵巢癌中的细胞迁移和侵袭

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作者:Meina Yan, Xinxin Yang, Rong Shen, Chengjiang Wu, Hui Wang, Qing Ye, Peifang Yang, Lubin Zhang, Miao Chen, Bing Wan, Qinqin Zhang, Sheng Xia, Xiaodong Lu, Genbao Shao, Xiaoming Zhou, Jun Yu, Qixiang Shao

Abstract

Epithelial ovarian carcinoma (EOC) is the most lethal gynecologic malignancy. However, the molecular mechanisms remain unclear. In this study, we found that miR-146b was downregulated in EOC and its expression level was negatively correlated with the pathological staging. Follow-up functional experiments illustrated that overexpression of miR-146b significantly inhibited cell migration and invasion, and increased cell proliferation, but it also improved the response to chemotherapeutic agents. Mechanistically, we demonstrated that miR-146b exerted its function mainly through inhibiting F-box and leucine-rich repeat protein 10 (FBXL10), and upregulated the Cyclin D1, vimentin (VIM), and zona-occludens-1 (ZO-1) expression in EOC. These findings indicate that miR-146b-FBXL10 axis is an important epigenetic regulation pathway in EOC. Low miR-146b may contribute to cancer progression from primary stage to advanced stage, and may be the promising therapeutic target of EOC.

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