Center for Molecular Medicine, Xiangya Hospital and Collaboration Innovation Center for Cancer Medicine, Central South University, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, China.
Center for Molecular Medicine, Xiangya Hospital and Collaboration Innovation Center for Cancer Medicine, Central South University, China; Key Laboratory of Molecular Radiation Oncology of Hunan Province, China.
Biochim Biophys Acta Mol Basis Dis. 2019 Jun 1;1865(6):1201-1213. doi: 10.1016/j.bbadis.2019.01.015. Epub 2019 Jan 16.
Viral noncoding RNAs (Epstein-Barr virus-encoded RNAs, EBERs) are believed to play a critical role in the progression of lymphoma and nasopharyngeal carcinoma (NPC). However, the accurate mechanisms accounting for their oncogenic function have not been elucidated, especially in terms of interaction between tumor cells and mesenchymal cells. Here, we report that, in addition to NPC cells, EBERs are also found in endothelial cells in Epstein-Barr virus (EBV)-infected NPC parenchymal tissues, which implicates NPC-derived extracellular vesicles (EVs) in transmitting EBERs to endothelial cells. In support of this hypothesis, we first ascertained if EBERs could be transferred to endothelial cells via EVs isolated from NPC culture supernatant. Then, we clarified that EVs-derived EBERs could promote angiogenesis through stimulation of VCAM-1 expression. Finally, we explored the involvement of EBER recognition by TLR3 and RIG-I in NPC angiogenesis. Our observations collectively illustrate the significance and mechanism of EVs-derived EBERs in angiogenesis and underlie the interaction mechanisms between EBV-infected NPC cells and the tumor microenvironment.
病毒非编码 RNA（EB 病毒编码的 RNA，EBERs）被认为在淋巴瘤和鼻咽癌（NPC）的进展中发挥关键作用。然而，其致癌功能的确切机制尚未阐明，特别是在肿瘤细胞与间充质细胞之间的相互作用方面。在这里，我们报告称，除 NPC 细胞外，EBERs 还存在于 EBV 感染的 NPC 实质组织中的内皮细胞中，这意味着 NPC 衍生的细胞外囊泡（EVs）将 EBERs 传递给内皮细胞。为了支持这一假设，我们首先确定 NPC 培养上清液中分离的 EV 是否可以将 EBER 转移到内皮细胞。然后，我们阐明 EV 衍生的 EBER 可通过刺激 VCAM-1 表达促进血管生成。最后，我们探讨了 EBV 感染的 NPC 细胞中 TLR3 和 RIG-I 对 EBER 识别的参与情况。我们的观察结果共同说明了 EV 衍生的 EBERs 在血管生成中的意义和机制，并阐明了 EBV 感染的 NPC 细胞与肿瘤微环境之间的相互作用机制。
