MiR‐150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1. Issue 1 (8th November 2012)

• Record Type: Journal Article
• Authors: Yokobori, Takehiko; Suzuki, Shigemasa; Tanaka, Naritaka; Inose, Takanori; Sohda, Makoto; Sano, Akihiko; Sakai, Makoto; Nakajima, Masanobu; Miyazaki, Tatsuya; Kato, Hiroyuki; Kuwano, Hiroyuki
• Is Part Of: Cancer science. Volume 104:Issue 1(2013:Jan.)
• Page Start: 48
• Page End: 54
• Publication Date: 2012-11-08
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12030
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12030-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 of <italic>miR‐150</italic> was lower in ESCC than in normal esophageal mucosa. Here, we focused on <italic>ZEB1, </italic> epithelial‐mesenchymal‐transition (EMT)‐inducer, as a target gene of <italic>miR‐150</italic> based on <italic>in silico</italic> predictions. The purpose of this study was to clarify the clinicopathological significance of <italic>miR‐150</italic> in ESCC, and to investigate <italic>miR‐150</italic>′s EMT‐regulatory ability. Quantitative RT‐PCR was used to evaluate <italic>miR‐150</italic> expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the <italic>in vitro</italic> and <italic>in vivo</italic> function of <italic>miR‐150</italic> via degradation of <italic>ZEB1</italic>. <italic>MiR‐150</italic> expression was significantly lower in cancer tissues compared to adjacent non‐cancerous tissues (<italic>P </italic><bold><</bold><italic> </italic>0.001). Low expression of <italic>miR‐150</italic> in ESCC contributed to malignant potential, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion, clinical staging, and poor prognosis (<italic>P </italic><bold><</bold><italic> </italic>0.05). <italic>In vitro</italic> assays showed that EMT‐inducer‐<italic>ZEB1</italic> is a new direct target of <italic>miR‐150</italic>. Moreover, <italic>miR‐150</italic> induced MET‐like changes in TE‐8 cells through ZEB1 degradation (<italic>e.g</italic>., 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 of <italic>ZEB1</italic> by <italic>miR‐150</italic> could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC. (<italic>Cancer Sci</italic> 2013; 104: 48–54)</p> </abstract>