Fang Yuan-Yuan, Tan Ming-Rong, Zhou Jian, Liang Li, Liu Xiao-Yun, Zhao Kun, Bao Er-Chen
Department of Gynaecology, Xu Zhou Maternal and Child Health Care Hospital, Xuzhou 221009, China.
Department of Operation Room, Xiangyang No 1 People's Hospital, Hubei University of Medicine, Xiangyang 441000, China.
Onco Targets Ther. 2019 Nov 18;12:9449-9458. doi: 10.2147/OTT.S181037. eCollection 2019.
Substantive studies have described the ectopic microRNAs as a determinant of the pathogenesis of endometrial cancer (EC). miR-214-3p has been reported to be significantly downregulated in EC tissues, and its overexpression has been shown to inhibit the proliferation, migration, and invasion of EC cells. Our study sought to explore the molecular mechanism underlying the inhibitory effect of miR-214-3p on metastasis of EC cells.
The expressions of miR-214-3p and TWIST1 in EC tissues and cells were detected by quantitative real-time PCR. Cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) were measured by transwell and Western blot analyses, respectively. The interaction between miR-214-3p and TWIST1 was confirmed by luciferase reporter assay. Xenograft tumor assay was performed to verify the role and underlying mechanism of miR-214-3p in EC in vivo.
miR-214-3p was downregulated and TWIST1 was upregulated in EC tissues and cells. miR-214-3p was negatively correlated with TWIST1 expression in EC tissues. Overexpression of miR-214-3p suppressed migration, invasion, and EMT in EC cells. TWIST1 was identified as a target of miR-214-3p in EC cells, and its overexpression significantly restored the inhibitory effects of miR-214-3p on cell migration, invasion, and EMT while its knockdown remarkably abolished miR-214-3p inhibitor-mediated promotion of progression of EC cells. Additionally, addition of miR-214-3p inhibited tumor growth by regulating EMT in vivo.
miR-214-3p suppressed the EMT and metastasis of EC cells by targeting TWIST1, providing a novel biomarker for treatment of EC.
大量研究已将异位微小RNA描述为子宫内膜癌（EC）发病机制的一个决定因素。据报道，miR-214-3p在EC组织中显著下调，其过表达已显示出抑制EC细胞的增殖、迁移和侵袭。我们的研究旨在探索miR-214-3p对EC细胞转移抑制作用的分子机制。
通过定量实时PCR检测EC组织和细胞中miR-214-3p和TWIST1的表达。分别通过Transwell和蛋白质免疫印迹分析测量细胞迁移、侵袭和上皮-间质转化（EMT）。通过荧光素酶报告基因检测证实miR-214-3p与TWIST1之间的相互作用。进行异种移植瘤实验以验证miR-214-3p在体内对EC的作用及其潜在机制。
miR-214-3p在EC组织和细胞中下调，而TWIST1上调。miR-214-3p与EC组织中TWIST1的表达呈负相关。miR-214-3p的过表达抑制了EC细胞的迁移、侵袭和EMT。TWIST1被确定为EC细胞中miR-214-3p的靶标，其过表达显著恢复了miR-214-3p对细胞迁移、侵袭和EMT的抑制作用，而其敲低则显著消除了miR-214-3p抑制剂介导的EC细胞进展促进作用。此外，添加miR-214-3p通过在体内调节EMT抑制肿瘤生长。
miR-214-3p通过靶向TWIST1抑制EC细胞的EMT和转移，为EC治疗提供了一种新的生物标志物。
