MicroRNA-125b Suppresses Ovarian Cancer Progression via Suppression of the Epithelial-Mesenchymal Transition Pathway by Targeting the SET Protein
MicroRNA-125b Suppresses Ovarian Cancer Progression via Suppression of the Epithelial-Mesenchymal Transition Pathway by Targeting the SET Protein
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MicroRNA-125 b通过靶向SET蛋白抑制上皮-间质转化途径抑制卵巢癌进展
DOI：
10.1159/000445642
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发表时间：
2016-07
影响因子：
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通讯作者：
Xiaoyan Ying;Kuang Wei;Zhe Lin;Yugui Cui;Jie Ding;Yun Chen;Boqun Xu
中科院分区：
文献类型：
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作者：
Xiaoyan Ying;Kuang Wei;Zhe Lin;Yugui Cui;Jie Ding;Yun Chen;Boqun Xu
背景/目的：MicroRNA-125 b（miR-125 b）在几种类型的癌症中过表达，并导致化疗耐药性。然而，其在上皮性卵巢癌中的作用仍不清楚。本研究的目的是确定miR-125 b与卵巢癌上皮间质转化（EMT）之间的关系。方法：对55例卵巢上皮性癌（EOC）患者进行回顾性分析。采用实时荧光定量聚合酶链反应（RT-PCR）检测miR-125 b的相对表达，Western blot检测SET和EMT相关指标的蛋白表达。使用荧光素酶报告基因测定证实了miR-125 b对SET的调节。使用体内转移模型评估miR-125 b对转移的作用。结果：miR-125 b在卵巢癌组织中的表达明显降低。miR-125 b在EOC细胞中的异位表达可显著抑制肿瘤的侵袭，miR-125 b的表达与EMT和SET的表达在体内外均呈负相关。机制研究确定SET是miR-125 b的直接靶点，并且在肿瘤迁移期间观察到的SET的下调受到miR-125 b过表达的影响。结论：miR-125 b通过靶向SET蛋白抑制EOC细胞迁移和侵袭，本研究可能为了解EOC的进展提供新的机制。
Background/Aims: MicroRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to chemotherapy resistance. However, its role in epithelial ovarian carcinoma remains unknown. The goal of this study was to identify the relationship between miR-125b and the epithelial-mesenchymal transition (EMT) in ovarian cancer. Methods: In total, 55patients with epithelial ovarian cancer (EOC) were included in our study. The relative expression of miR-125b was measured using real-time polymerase chain reaction (RT-PCR).The protein expression of SET and EMT-related indicators in cell lines were assessed by Western blot. The regulation of SET by miR-125b was confirmed using luciferase reporter assays. The effect of miR-125b on metastasis was evaluated using an in vivo metastasis model. Results: miR-125b expression was markedly lower in the EOC specimens. Ectopic expression of miR-125b in EOC cells significantly inhibited tumor invasion.miR-125b expression was negatively associated with both EMT and SET expression, in vivo and in vitro. Mechanistic studies identified SET as a direct target of miR-125b, and the downregulation of SET, observed during tumor migration, was affected by the overexpression of miR125b. Conclusion: miR-125b suppresses EOC cell migration and invasion by targeting the SET protein, and this study may provide a novel mechanism for understanding the progression of EOC.