...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells
【24h】

A Repertoire of MicroRNAs Regulates Cancer Cell Starvation by Targeting Phospholipase D in a Feedback Loop That Operates Maximally in Cancer Cells

机译：MicroRNA的全部功能通过靶向磷脂酶D在最大程度地在癌细胞中运作的反馈环中调节癌细胞饥饿。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

We report a negative feedback loop between the signaling protein phospholipase D (PLD), phosphatidic acid (PA), and a specific set of microRNAs (miRNAs) during nutrient starvation of breast cancer cells. We show that PLD expression is increased in four breast cancer cell lines and that hypoxia, cell overcrowding, and nutrient starvation for 3 to 6 h increase expression even further. However, after prolonged (>12-h) starvation, PLD levels return to basal or lower levels. The mechanism for this is as follows. First, during initial starvation, an elevated PA (the product of PLD enzymatic activity) activates mTOR and S6K, known to inhibit apoptosis, and enhances cell migration especially in post-epithelial-to-mesenchymal transition (post-EMT) cancer cells. Second, continued PA production in later starvation induces expression of PLD-targeting microRNA 203 (miR-203), miR-887, miR-3619-5p, and miR-182, which reduce PLD translation. We provide direct evidence for a feedback loop, whereby PLD induction upon starvation leads to PA, which induces expression of miRNAs, which in turn inhibits PLD2 translation. The physiological relevance for breast cancer cells is that as PA can activate cell invasion, then, due to the negative feedback, it can deprive mTOR and S6K of their natural activator. It can further prevent inhibition of apoptosis and allow cells to survive nutrient deprivation, which normal cells cannot do.
机译：我们报告乳腺癌细胞营养缺乏期间信号蛋白磷脂酶D（PLD），磷脂酸（PA）和一组特定的microRNA（miRNA）之间的负反馈循环。我们显示PLD表达在四个乳腺癌细胞系中增加，并且缺氧，细胞过度拥挤和营养不足持续3至6小时进一步增加了表达。但是，长期饥饿（> 12小时）后，PLD含量恢复到基础或更低水平。其机制如下。首先，在最初的饥饿期间，升高的PA（PLD酶活性的产物）激活了mTOR和S6K（已知抑制凋亡），并增强了细胞迁移，尤其是在上皮后向间质转化（EMT后）癌细胞中。其次，在以后的饥饿中继续产生PA会诱导靶向PLD的microRNA 203（miR-203），miR-887，miR-3619-5p和miR-182的表达，从而减少PLD翻译。我们为反馈回路提供了直接的证据，饥饿时PLD诱导导致PA诱导PA，后者诱导miRNA的表达，进而抑制PLD2翻译。与乳腺癌细胞的生理相关性在于，PA可以激活细胞入侵，因此，由于负反馈，它可以剥夺mTOR和S6K的天然激活剂。它可以进一步防止凋亡的抑制，并使细胞在营养缺乏的情况下存活，而正常细胞则无法做到。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
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