Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.
Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.
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Epstein-Barr病毒编码的microRNA BART1通过调节鼻咽癌中PTEN依赖性通路诱导肿瘤转移
DOI：
10.1038/ncomms8353
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发表时间：
2015-07-02
影响因子：
16.6
通讯作者：
Li X
中科院分区：
文献类型：
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作者：
Cai L;Ye Y;Jiang Q;Chen Y;Lyu X;Li J;Wang S;Liu T;Cai H;Yao K;Li JL;Li X
EB病毒（Epstein-Barr virus，EBV）是第一个发现的编码多种miRNAs的人类病毒，与鼻咽癌（nasopharyngeal carcinoma，NPC）的病因有关。然而，这些病毒miRNAs如何精确调节NPC中的肿瘤转移仍然不清楚。本文报道了EBV-miR-BART 1在鼻咽癌组织中的高表达，并与鼻咽癌的病理及临床分期密切相关。EBV-miR-BART 1表达的改变导致NPC细胞体外迁移和侵袭的增加，并导致体内肿瘤转移。在机制上，EBV-miR-BART 1直接靶向细胞肿瘤抑制因子PTEN。通过EBV-miR-BART 1减少PTEN剂量激活PTEN依赖性通路，包括PI 3 K-Akt、FAK-p130 Cas和Shc-MAPK/ERK 1/2信号传导，驱动EMT，并因此增加NPC细胞的迁移、侵袭和转移。PTEN的重建挽救了由EBV-miR-BART 1产生的所有表型，突出了PTEN在NPC中EBV-miR-BART驱动的转移中的作用。我们的研究结果为EB病毒调控鼻咽癌转移提供了新的见解，并为制定针对鼻咽癌的临床干预策略提供了依据。 EB病毒与鼻咽癌有关，以前的研究集中在病毒蛋白在肿瘤病理学中的作用。在这里，作者表明病毒miRNA靶向宿主蛋白PTEN，并通过驱动肿瘤转移在鼻咽癌晚期发挥关键作用。
Epstein–Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130Cas and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC. Epstein–Barr virus is associated with nasopharyngeal carcinoma and previous studies have focused on the role of viral proteins in tumour pathology. Here, the authors show that a viral miRNA targets the host protein PTEN and has a critical role in the late stage of nasopharyngeal carcinoma by driving tumour metastasis.