Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma

Cong,Ningning; Du,Ping; Zhang,Anling; Shen,Fajuan; Su,Juan; Pu,Peiyu; Wang,Tao; Zjang,Jie; Kang,Chunsheng; Zhang,Qingyu

doi:10.3892/or.2013.2267

Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma

Authors:
- Ningning Cong
- Ping Du
- Anling Zhang
- Fajuan Shen
- Juan Su
- Peiyu Pu
- Tao Wang
- Jie Zjang
- Chunsheng Kang
- Qingyu Zhang
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Affiliations: Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, P.R. China
Published online on: January 31, 2013 https://doi.org/10.3892/or.2013.2267
Pages: 1579-1587

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Abstract

In a previous study, we found that microRNA (miRNA)-200a suppresses Wnt/β-catenin signaling by interacting with β-catenin, thereby inhibiting migration, invasion and proliferation. However, the mechanism involved in this suppression remains unclear. In the present study, we investigated the underlying mechanism of miR-200a regulation of epithelial-mesenchymal transition (EMT) in gastric carcinoma cells, and confirmed the tumor suppressor role of miR-200a in vivo. The expressions of miRNA-200a, -200b and -200c, identified by fluorescent in situ hybridization, were downregulated and inversely correlated with WHO grades of gastric adenocarcinoma (GA). The expression of the potential miR-200a target genes ZEB1 and ZEB2 was detected immunohistochemically. These examinations used the same tissue microarrays to analyze the relationships between miR-200a and potential target genes. The expression of miR-200a and ZEB1/ZEB2 in the same GA tissue microarrays was inversely related. Restored miR-200a expression inhibited tumor growth in nude mice harboring subcutaneous SGC7901 xenografts. The expression of N-cadherin, β-catenin, Twist1 and Snail2 decreased, and E-cadherin levels increased, when miR-200a was elevated, as tested by fluorescence microscopy and immunohistochemistry. Similar results were observed in vivo. We found upregulated miR-200a expression to increase E-cadherin and suppress the Wnt/β-catenin pathway by targeting ZEB1 and ZEB2 in GA, thus delaying tumor growth in vivo. The effect of miR-200a on Wnt/β-catenin signaling may provide a therapeutic target against EMT.

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