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MiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducers ZEB1

icecream 添加于 2012-10-14 09:59 | 1069 次阅读 | 0 个评论
  •  作 者

    Yokobori T, Suzuki S, Tanaka N, Inose T, Sohda M, Sano A, Sakai M, Nakajima M, Miyazaki T, Kato H, Kuwano H
  •  摘 要

    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 miR-150 was lower in ESCC than in normal esophageal mucosa. Here, we focused on ZEB1, epithelial-mesenchymal-transition (EMT)-inducers, as target genes of miR-150 based on in silico predictions. The purpose of this study was to clarify the clinicopathological significance of miR-150 in ESCC, and to investigate miR-150's EMT-regulatory ability. Quantitative RT-PCR was used to evaluate miR-150 expression in 108 curative resected ESCC samples to determine the clinicopathological significance. Moreover, we examined the in vitro and in vivo function of miR-150 via degradation of ZEB1. MiR-150 expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (p<0.001). Low expression of miR-150 in 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 vitro assays showed that EMT-inducer-ZEB1 is a new direct target of miR-150. Moreover, miR-150 induced 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 of ZEB1 by miR-150 could provide new insights into preventing metastasis and also suggests novel targeted therapeutic strategies in ESCC.
  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: Cancer Science
    • 期刊缩写: Cancer Sci
    • 期卷页: 2012
    • 地址: Department of General Surgical Science, Gunma University, Graduate School of Medicine
    • ISBN: 1347-9032
  • 学科领域 生物医药 » 预防卫生学

  • 相关链接 DOI URL 

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