Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma

Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma
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DOI:
10.2147/ott.s191041
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发表时间:
2019-01-01
影响因子:
4
通讯作者:
Zheng, Jing
Zheng, Jing
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Changmin;Xu, Jiqin;Zheng, Jing

文献摘要

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背景:子宫内膜癌(endometrialcarcinoma,EC)是世界范围内最常见、最致命的恶性肿瘤. Syncytin-1在多种类型的癌症中表达。材料与方法:选取滨州医学院130例原发性食管癌标本,采用不同病理分期的食管癌组织,分析syncytin-1在食管癌中的表达,探讨syncytin-1在食管癌中的作用。采用Kaplan-Meier法分析EC患者的总生存期。通过Western印迹分析HECCL-1和RL-95-2细胞中合胞素-1的表达。采用细胞计数试剂盒-8、流式细胞仪和transwell法检测细胞的增殖、周期、迁移和侵袭能力。结果:Syncytin-1在EC组织和细胞中表达上调,并与EC的临床分期、ER、Ki-67表达及总生存期有关。功能研究表明,syncytin-1过表达可促进EC细胞增殖、细胞周期进程以及迁移和侵袭。抑制合胞素-1的表达也抑制细胞增殖和凋亡。合胞素-1的表达显著提高了EMT相关基因(波形蛋白、E-钙粘蛋白、蛞蝓和ZEB 1)的表达水平,但显著降低了上皮标志物(N-钙粘蛋白和蜗牛)的表达水平。此外,我们发现syncytin-1与AKT相关基因(total-AKT,p-AKT和vinculin)不相关。结论:我们的研究结果表明,syncytin-1可能促进攻击行为,并可作为一种新的预后生物标志物EC。我们的研究为EMT信号的调控机制提供了新的见解。
Background: Endometrial carcinoma (EC) is the most common and lethal malignancy worldwide. Syncytin-1 is expressed in multiple types of cancer. However, the expression A-pattern and potential mechanism of syncytin-1 and its clinical significance in EC remain unclear.Materials and methods: We analyzed 130 primary EC specimens from Binzhou Medical University to investigate the clinical role of syncytin-1 in EC by using different advanced pathological stages of EC tissues. Kaplan-Meier analysis was used to measure the overall survival of EC patients. Syncytin-1 expression was analyzed by Western blot assays in HECCL-1 and RL-95-2 cells. Cell proliferation, cycle, migration, and invasion abilities were detected by cell counting kit-8, flow cytometry, and transwell assays. AKT and epithelial-mesenchymal transition (EMT)-related genes were assessed by Western blot assays in HECCL-1 and RL-95-2 cells.Results: Syncytin-1 was upregulated in EC tissues and cells and was related to clinical stages, expression of ER, Ki-67, and overall survival of EC. Functional research revealed that overexpression of syncytin-1 can promote cell proliferation, cell cycle progression, and the migration and invasion of EC cells. Suppression of syncytin-1 expression also inhibited cell proliferation and apoptosis in vitro. The expression of syncytin-1 substantially improved the expression levels of EMT-related genes (vimentin, E-cadherin, slug, and ZEB1) but significantly decreased those of epithelial markers (N-cadherin and snail). In addition, we found that syncytin-1 was not correlated with AKT-related genes (total-AKT, p-AKT, and vinculin).Conclusion: Our results suggested that syncytin-1 may promote aggressive behavior and can serve as a novel prognostic biomarker for EC. Our study provides new insights into the regulatory mechanism of EMT signaling.