He Baoyu, Li Weiming, Wu Yingfen, Wei Fang, Gong Zhaojian, Bo Hao, Wang Yumin, Li Xiayu, Xiang Bo, Guo Can, Liao Qianjin, Chen Pan, Zu Xuyu, Zhou Ming, Ma Jian, Li Xiaoling, Li Yong, Li Guiyuan, Xiong Wei, Zeng Zhaoyang
The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Cell Death Dis. 2016 Sep 1;7(9):e2353. doi: 10.1038/cddis.2016.253.
Epstein-Barr virus (EBV) infection is causatively related to a variety of human cancers, including nasopharyngeal carcinoma (NPC) and gastric cancer (GC). EBV encodes 44 mature miRNAs, a number of which have been proven to promote carcinogenesis by targeting host genes or self-viral genes. However, in this study, we found that an EBV-encoded microRNA, termed EBV-miR-BART6-3p, inhibited EBV-associated cancer cell migration and invasion including NPC and GC by reversing the epithelial-mesenchymal transition (EMT) process. Using microarray analysis, we identified and validated that a novel long non-coding RNA (lncRNA) LOC553103 was downregulated by EBV-miR-BART6-3p, and LOC553103 knockdown by specific siRNAs phenocopied the effect of EBV-miR-BART6-3p, while LOC553103 overexpression promoted cancer cell migration and invasion to facilitate EMT. In conclusion, we determined that EBV-miR-BART6-3p, a microRNA encoded by oncogenic EBV, inhibited EBV-associated cancer cell migration and invasion by targeting and downregulating a novel lncRNA LOC553103. Thus, our study presents an unreported mechanism underlying EBV infection in EBV-associated cancer carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC and other EBV-related cancers.
爱泼斯坦-巴尔病毒（EBV）感染与多种人类癌症相关，包括鼻咽癌（NPC）和胃癌（GC）。EBV编码44种成熟的微小RNA（miRNA），其中一些已被证明可通过靶向宿主基因或自身病毒基因来促进肿瘤发生。然而，在本研究中，我们发现一种名为EBV-miR-BART6-3p的EBV编码的微小RNA，通过逆转上皮-间质转化（EMT）过程，抑制了包括NPC和GC在内的EBV相关癌细胞的迁移和侵袭。通过微阵列分析，我们鉴定并验证了一种新型长链非编码RNA（lncRNA）LOC553103被EBV-miR-BART6-3p下调，并且通过特异性小干扰RNA（siRNA）敲低LOC553103可模拟EBV-miR-BART6-3p的作用，而LOC553103的过表达促进癌细胞迁移和侵袭以促进EMT。总之，我们确定由致癌性EBV编码的微小RNA EBV-miR-BART6-3p通过靶向和下调新型lncRNA LOC553103来抑制EBV相关癌细胞的迁移和侵袭。因此，我们的研究提出了EBV感染在EBV相关癌症发生过程中一种未报道的机制，并为NPC和其他EBV相关癌症提供了一种潜在的新型诊断和治疗生物标志物。
