title: 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.
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.
authors: Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
authors: Ningning
authors: N
authors: Cong
authors: Ping
authors: P
authors: Du
authors: Anling
authors: A
authors: Zhang
authors: Fajuan
authors: F
authors: Shen
authors: Juan
authors: J
authors: Su
authors: Peiyu
authors: P
authors: Pu
authors: Tao
authors: T
authors: Wang
authors: Jie
authors: J
authors: Zjang
authors: Chunsheng
authors: C
authors: Kang
authors: Qingyu
authors: Q
authors: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1