• Xiaokang Tian, Qian Fei, Mingyu Du, Hongming Zhu, Jinjun Ye, Luxi Qian, Zhiwei Lu, Wenjun Zhang, Yan Wang, Fanyu Peng, Jie Chen, Baoling Liu, Qian Li, Xia He, and Li Yin.
• Xuzhou Medical University, Xuzhou, Jiangsu, China.
• Cancer Med. 2019 Mar 1; 8 (3): 1197-1208.

AbstractMetastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR-130a-3p in the progression of transforming growth factor-β (TGF-β)-induced EMT in vivo and in vitro. The expression of miR-130a-3p in ESCC cell line and normal esophageal epithelial cell was determined by RT-qPCR. The protein expression levels of TGF-β-induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual-luciferase report assays were used to validate the regulation of miR-130a-3p-SMAD4 axis. The effect of miR-130a-3p and SMAD4 in TGF-β-induced migration, invasion in the ESCC cell line EC-1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF-β-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. miR-130a-3p, which directly targets SMAD4, is down-regulated in ESCC. miR-130a-3p inhibits the migration and invasion of EC-1 cells both in vitro and in vivo. Finally, miR-130a-3p inhibits TGF-β-induced EC-1 cell migration, invasion, and EMT progression in a SMAD4-dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF-β/miR-130a-3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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