Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling
Downregulation of ABI2 expression by EBV-miR-BART13-3p induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells through upregulation of c-JUN/SLUG signaling
复制标题
EBV-miR-BART13-3p下调ABI2表达通过上调c-JUN/SLUG信号诱导鼻咽癌细胞上皮-间质转化
DOI：
10.18632/aging.102618
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发表时间：
2020-01-15
期刊：
影响因子：
5.2
通讯作者：
Yang, Kunyu
中科院分区：
文献类型：
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作者：
Huang, Jing;Qin, You;Yang, Kunyu
现有证据表明，循环中的EB病毒（EBV）-miR-BART13-3p在鼻咽癌（NPC）患者血浆中高表达，尤其是在晚期疾病患者中。然而，EBV-miR-BART13-3p 在 NPC 发展中所起的确切作用仍知之甚少。在这里，我们发现EBV-miR-BART13-3p的上调表达导致NPC细胞体外迁移和侵袭能力增加，并导致体内肿瘤转移。此外，我们发现EBV-miR-BART13-3p直接靶向ABI2，被称为肿瘤抑制因子和细胞迁移抑制剂，通过激活c-JUN/SLUG信号通路驱动上皮间质转化（EMT）。沉默 ABI2 显示出与 EBV-miR-BART13-3p 过表达相似的效果，而 ABI2 的重建导致表型逆转，突出了 ABI2 在 EBV-miR-BART13-3p 驱动的 NPC 转移中的作用。此外，鼻咽癌组织样本中ABI2的表达水平与鼻咽癌患者的N分期相关。综上所述，这些结果表明了一种新机制，即 EBV-miR-BART13-3p 下调 ABI2 通过上调 c-JUN/SLUG 信号通路促进鼻咽癌的 EMT 和转移。
Existing evidence has shown that circulating Epstein-Barr virus (EBV)-miR-BART13-3p is highly expressed in plasma of nasopharyngeal carcinoma (NPC) patients, especially among patients with advanced diseases. However, the exact role that EBV-miR-BART13-3p plays in the development of NPC remains poorly understood. Here we show that up-regulated expression of EBV-miR-BART13-3p leads to increased capacity in migration and invasion of NPC cells in vitro and causes tumor metastasis in vivo. Furthermore, we find that EBV-miR-BART13-3p directly targets ABI2, known as a tumor suppressor and a cell migration inhibitor, drives epithelial-mesenchymal transition (EMT) by activating c-JUN/SLUG signaling pathway. Silencing ABI2 shows similar effects to overexpression of EBV-miR-BART13-3p, whereas reconstitution of ABI2 resulted in a phenotypic reversion, highlighting the role of ABI2 in EBV-miR-BART13-3p-driven metastasis in NPC. Besides, expression levels of ABI2 in NPC tissue samples correlate with N stages of NPC patients. Taken together, these results suggest a novel mechanism by which ABI2 downregulation by EBV-miR-BART13-3p promotes EMT and metastasis of NPC via upregulating c-JUN/SLUG signaling pathway.