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.
Background
Cervical cancer is a malignancy that’s common in female with high incidence and mortality worldwide. MicroRNAs (miRNAs) act a pivotal part in human cancer development. Our aim was to investigate the effect of miR-126 on cervical cancer and its underlying molecular mechanism.
Results
Firstly, RT-qPCR assay revealed that the expression of miR-126 was significantly downregulated in cervical cancer tissues and cell lines, compared with that in normal adjacent tissues and normal cervical epithelial cell line (Ect1/E6E7), respectively. Then, ZEB1 was verified as a target of miR-126 by using luciferase reporter assay. Inversely, the expression of ZEB1 was markedly upregulated in tumor tissues, and its mRNA level was negatively regulated by miR-126 expression in SiHa and Hela cells. Moreover, the capability of cell proliferation, migration and invasion was analyzed by CCK-8, wound healing assay and transwell assay, respectively. The results demonstrated that overexpression of miR-126 inhibited SiHa and Hela cell proliferation, migration and invasion, while ZEB1 abolished the inhibition induced by miR-126. Additionally, miR-126 suppressed MMP2 and MMP9 in mRNA and protein levels, as well as inhibited the protein expression of p-JAK2 and p-STAT3 in both SiHa and Hela cells, while ZEB1 rescued miR-126-induced suppression.
Conclusion
miR-126 functions as a tumor suppressor in cervical cancer cells in vitro, which inhibits the proliferation, migration and invasion by suppressing MMP2, MMP9 expression and inactivating JAK2/STAT3 signaling pathway through targeting ZEB1, suggesting that miR-126 might be a novel potential target for the diagnosis and treatment of patients with cervical cancer.
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