MiR-150is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducerZEB1

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Abstract

The association of microRNAs (miRs) with cancer progression has been established in many cancers including esophageal squamous cell carcinoma (ESCC). A public microarray database showed that the expression ofmiR-150was lower in ESCC than in normal esophageal mucosa. Here, we focused onZEB1,epithelial-mesenchymal-transition (EMT)-inducer, as a target gene ofmiR-150based onin silicopredictions. The purpose of this study was to clarify the clinicopathological significance ofmiR-150in ESCC, and to investigatemiR-150′s EMT-regulatory ability. Quantitative RT-PCR was used to evaluatemiR-150expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined thein vitroandin vivofunction ofmiR-150via degradation ofZEB1.MiR-150expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P< 0.001). Low expression ofmiR-150in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (P< 0.05).In vitroassays showed that EMT-inducer-ZEB1is a new direct target ofmiR-150. Moreover,miR-150induced MET-like changes in TE-8 cells through ZEB1 degradation (e.g., E-cadherin expression, vimentin repression, epithelial morphology, and suppression of migration ability), and significantly inhibited tumorigenicity and tumor growth in a mouse xenograft model. Analysis of the regulation ofZEB1bymiR-150could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC. (Cancer Sci2013; 104: 48–54)

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