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microRNA-1228*impairs the pro-angiogenic activity of gastric cancer cells by targeting macrophage migration inhibitory factor

机译：MicroRNA-1228 *通过靶向巨噬细胞迁移抑制因子损害胃癌细胞的促血管生成活性

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摘要

Our previous study has shown that microRNA-1228* (miR-1228*) is downregulated in gastric cancer tissues and restoration of its expression retards tumor growth in a gastric cancer xenograft model. In this work, we aimed to explore the role of miR-1228* in gastric cancer cell cycle progression and angiogenesis and to identify its functional target gene(s). It was found that miR-1228* overexpression significantly inhibited the proliferation and colony formation of gastric cancer cells, compared to vector-transfected cells. As determined by propidium iodide staining, overexpression of miR-1228* resulted in an enrichment of G0/G1 phase cells in gastric cancer cells. miR-1228*-overexpressing cells showed a significant reduction of vascular endothelial growth factor expression and secretion. Conditioned media from miR-1228*-overexpressing cells showed a reduced capacity to promote endothelial cell migration and tube formation. Mechanistically, macrophage migration inhibitory factor (MIF) was identified as a direct target gene of miR-1228*. Enforced expression of MIF rescued gastric cancer cells from miR-1228*-mediated suppression of proliferation and angiogenesis. In vivo xenograft mouse studies further demonstrated that co-expression of MIF with miR-1228* in gastric cancer cells significantly restored tumor growth and increased microvascular density. Taken together, miR-1228* acts as a negative regulator of gastric cancer growth and angiogenesis through downregulation of MIF. This work suggests miR-1228* as a potential target for anti-angiogenic therapy against gastric cancer. (C) 2017 Elsevier Inc. All rights reserved.
机译：我们以前的研究表明，MicroRNA-1228 *（miR-1228 *）下调在胃癌组织中，并恢复其表达延迟胃癌异种移植模型中的肿瘤生长。在这项工作中，我们旨在探讨miR-1228 *在胃癌细胞周期进展和血管生成中的作用，并鉴定其功能靶基因。结果发现，与载体转染细胞相比，miR-1228 *过表达显着抑制胃癌细胞的增殖和菌落形成。通过碘化钛染色来确定MiR-1228 *的过表达导致胃癌细胞中的G0 / G1相细胞富集。 miR-1228 * -Overxpressing细胞显示血管内皮生长因子表达和分泌显着降低。来自miR-1228 * -overxpressing细胞的调节介质显示出促进内皮细胞迁移和管形成的能力降低。机械地，巨噬细胞迁移抑制因子（MIF）被鉴定为miR-1228 *的直接靶基因。 MIR-1228的MIF的强制表达来自miR-1228 *介导的增殖和血管生成的抑制。体内异种移植鼠标研究进一步证明了MIF与mif-1228 *在胃癌细胞中的联合表达显着恢复了肿瘤生长和微血管密度增加。一起携带MiR-1228 *通过MIF的下调作为胃癌生长和血管生成的负调节剂。这项工作表明miR-1228 *作为胃癌抗血管生成治疗的潜在目标。 （c）2017年Elsevier Inc.保留所有权利。

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  • 来源
    《Life sciences》 |2017年第2017期|共8页
  • 作者

    Jia Litao; Chen Jiamin; Xie Chuangao; Shao Liming; Xu Zhipeng; Zhang Lu;

  • 作者单位

    Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Gastroenterol Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Gastroenterol Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Gastroenterol Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Gastroenterol Hangzhou Zhejiang Peoples R China;

    Zhejiang Univ Sch Med Affiliated Hosp 2 Dept Gastroenterol Hangzhou Zhejiang Peoples R China;

    Zhejiang Chinese Med Univ Affiliated Hosp 1 Dept Gastroenterol 54 Youdian Rd Hangzhou 310006;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医药、卫生;
  • 关键词

    Angiogenesis; Gastric cancer; Growth; microRNA; MIF;

    机译：血管生成;胃癌;生长;microRNA;MIF;

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