EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma
EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma
复制标题
EBV-miR-BART1-5P通过PTEN独立方式激活AMPK/mTOR/HIF1通路，促进鼻咽癌中的糖酵解和血管生成。
DOI：
10.1371/journal.ppat.1007484
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发表时间：
2018-12-01
期刊：
影响因子：
6.7
通讯作者：
Li, Xin
中科院分区：
文献类型：
--
作者：
Lyu, Xiaoming;Wang, Jianguo;Li, Xin
代谢异常和血管生成失控是恶性肿瘤的两个重要特征。这两个事件的发生涉及许多关键的分子变化，包括miRNA。然而，EBV编码的miRNA很少被提及能够调节肿瘤代谢和肿瘤血管生成。本文报道了EBV编码的关键miRNAs之一EBV-miR-Bart 1 - 5 P在体外和体内均能显著促进鼻咽癌（NPC）细胞糖酵解并诱导血管生成。EBV-miR-Bart 1 - 5 P直接作用于AMPK α 1，调节AMPK/mTOR/HIF 1通路，促使NPC细胞发生异常有氧糖酵解和血管生成，最终导致NPC生长失控。我们的研究结果为鼻咽癌的代谢和血管生成提供了新的见解，并为未来鼻咽癌靶向治疗的发展提供了新的机会。
Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis. Here, we reported that one of the key miRNAs encoded by EBV, EBV-miR-Bart1-5P, can significantly promote nasopharyngeal carcinoma (NPC) cell glycolysis and induces angiogenesis in vitro and in vivo. Mechanistically, EBV-miR-Bart1-5P directly targets the alpha 1 catalytic subunit of AMP-activated protein kinase (AMPK alpha 1) and consequently regulates the AMPK/mTOR/HIF1 pathway which impelled NPC cell anomalous aerobic glycolysis and angiogenesis, ultimately leads to uncontrolled growth of NPC. Our findings provide new insights into metabolism and angiogenesis of NPC and new opportunities for the development of targeted NPC therapy in the future.