...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleic Acids Research >HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway
【24h】

HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway

机译：HIV-1 NEF和KSHV oncogene K1通过诱导蜂窝MIR-718来调节PTEN / AKT / MTOR信号传导途径来协同促进血管生成

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Kaposi's sarcoma (KS) is an AIDS-defining cancer with aberrant neovascularization caused by KS-associated herpesvirus (KSHV). Although the interaction between HIV-1 and KSHV plays a pivotal role in promoting the aggressive manifestations of KS, the pathogenesis underlying AIDS-KS remains largely unknown. Here we examined HIV-1 Nef protein promotion of KSHV oncoprotein K1-induced angiogenesis. We showed that both internalized and ectopic expression of Nef in endothelial cells synergized with K1 to facilitate vascular tube formation and cell proliferation, and enhance angiogenesis in a chicken CAM model. In vivo experiments further indicated that Nef accelerated K1-induced angiogenesis and tumorigenesis in athymic nu/nu mice. Mechanistic studies revealed that Nef and K1 synergistically activated PI3K/AKT/mTOR signaling by downregulating PTEN. Furthermore, Nef and K1 induced cellular miR-718, which inhibited PTEN expression by directly targeting a seed sequence in the 3' UTR of its mRNA. Inhibition of miR-718 expression increased PTEN synthesis and suppressed the synergistic effect of Nef- and K1-induced angiogenesis and tumorigenesis. These results indicate that, by targeting PTEN, miR-718 mediates Nef- and K1-induced angiogenesis via activation of AKT/mTOR signaling. Our results demonstrate an essential role of miR-718/AKT/mTOR axis in AIDS-KS and thus may represent an attractive therapeutic target.
机译：Kaposi的Sarcoma（KS）是艾滋病界定癌症，其具有异常新生血管引起的ks相关的herpesvirus（Kshv）。虽然HIV-1和KSHV之间的相互作用在促进Ks的侵袭性表现方面发挥了枢转作用，但潜在的艾滋病-Ks的发病机制仍然未知。在这里，我们检查了KSHV癌蛋白K1诱导的血管生成的HIV-1 NEF蛋白促进。我们表明，Nef中的内皮细胞内化和异位表达均用K1协同促进血管管形成和细胞增殖，并增强鸡凸轮模型中的血管生成。体内实验进一步表明Nef加速了胸腺诺/ Nu小鼠中的K1诱导的血管生成和肿瘤发生。机械研究表明，NEF和K1通过下调PTEN来协同激活PI3K / AKT / MTOR信号传导。此外，NEF和K1诱导细胞miR-718，其通过直接靶向其mRNA的3'UTR中的种子序列来抑制PTEN表达。 miR-718表达的抑制增加了PTEN合成，抑制了Nef和K1诱导的血管生成和肿瘤发生的协同作用。这些结果表明，通过靶向PTEN，MIR-718通过激活AKT / MTOR信号传导介导NEF和K1诱导的血管生成。我们的结果表明MIR-718 / AKT / MTOR轴在艾滋病-Ks中的重要作用，因此可以代表一种有吸引力的治疗目标。

著录项

  • 来源
    《Nucleic Acids Research》 |2014年第15期|共18页
  • 作者

    Xue Min; Yao Shuihong; Hu Minmin; Li Wan; Hao Tingting; Zhou Feng; Zhu Xiaofei; Lu Hongmei; Qin Di; Yan Qin; Zhu Jianzhong; Gao Shou-Jiang; Lu Chun;

  • 作者单位

    Nanjing Med Univ State Key Lab Reprod Med Nanjing Jiangsu Peoples R China;

    Quzhou Coll Technol Sch Med Quzhou 324000 Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Affiliated Hosp 1 Dept Obstet Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Nanjing Med Univ Dept Microbiol Nanjing 210029 Jiangsu Peoples R China;

    Univ Pittsburgh Inst Canc Canc Virol Program Pittsburgh PA 15232 USA;

    Univ So Calif Keck Sch Med Dept Mol Microbiol &

    Immunol Los Angeles CA 90033 USA;

    Nanjing Med Univ State Key Lab Reprod Med Nanjing Jiangsu Peoples R China;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

相似文献

  • 外文文献
  • 中文文献
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号