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

Authors Liu C, Xu J, Wen F, Yang F, Li X, Geng D, Li L, Chen J, Zheng J

Received 16 October 2018

Accepted for publication 21 November 2018

Published 17 December 2018 Volume 2019:12 Pages 31—40

DOI https://doi.org/10.2147/OTT.S191041

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su


Changmin Liu,1,* Jiqin Xu,2,* Feifei Wen,3 Fangfang Yang,1 Xiaoming Li,4 Dianzhong Geng,1 Lei Li,1 Jiming Chen,5 Jing Zheng6

1Department of Oncology, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China; 2Department of Obstetrics and Gynecology, Shuyang People’s Hospital, Affiliated to Xuzhou Medical University, Jiangsu, China; 3Department of Pathology, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China; 4Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China; 5Department of Obstetrics and Gynecology, The Affiliated Changzhou No 2 People’s Hospital of Nanjing Medical University, Changzhou 213000, Jiangsu, China; 6Department of Clinical Medicine Laboratory, Binzhou Medical University Hospital, Binzhou 256603, Shandong, China

*These authors contributed equally to this work

Background: Endometrial carcinoma (EC) is the most common and lethal malignancy worldwide. Syncytin-1 is expressed in multiple types of cancer. However, the expression ­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.

Keywords: syncytin-1, epithelial-mesenchymal transition, endometrial carcinoma

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