EBV-miR-BART22通过激活Wnt/β-catenin信号通路促进鼻咽癌转移的作用与机制

Epstein–Barr virus (EBV) has been reported to promote the metastasis of nasopharyngeal carcinoma (NPC). Recently, we found that EBV encoded miR-BART22 (EBV-miR-BART22) specific expressed in the NPC tissues and positively associated with tumor clinical stage. Preliminary experimental results revealed that over-expression of EBV-miR-BART22 in EBV-negative nasopharyngeal carcinoma cell line 5-8F promoting the cells migration ability and β-catenin translocated into nuclear, whereas interfered EBV-miR-BART22 in the EBV-positive nasopharyngeal carcinoma cell line C666 could inhibit the cells migration ability and β-catenin translocated into nuclear. All of these results suggest that EBV-miR-BART22 could promote the metastasis of nasopharyngeal carcinoma cells through activating the Wnt/β-catenin signaling pathway. Based on the preliminary work above, we intends to utilize the clinical specimens, in vivo animal models and in vitro cellular models: ①To confirm the EBV-miR-BART22 induces the metastasis of NPC. ②To clarify the target genes and key signaling pathways involved in the EBV-miR-BART22 facilitated metastasis of nasopharyngeal carcinoma cells. The present study is aims to clarify the molecular mechanism by which EBV-miR-BART22 promoted NPC metastasis, thus providing a promising new intervention target for the treatment of NPC metastasis.

研究表明EB病毒具有促进鼻咽癌转移的作用。我们最近研究发现EB病毒编码的miR-BART22(EBV-miR-BART22)在鼻咽癌组织特异性表达，且表达水平与肿瘤临床分期正相关。预实验结果表明过表达EBV-miR-BART22促进EBV阴性鼻咽癌细胞株5-8F的迁移和β-catenin入核，而在EBV阳性鼻咽癌细胞株C666干扰EBV-miR-BART22抑制细胞迁移和β-catenin入核。以上结果提示EBV-miR-BART22可能通过激活Wnt/β-catenin信号通路促进鼻咽癌细胞转移。本项目拟利用临床标本、体内动物模型和体外细胞模型：①证实EBV-miR-BART22诱发鼻咽癌细胞转移；②阐明EBV-miR-BART22促进鼻咽癌细胞转移的关键信号通路及靶基因。本研究旨在阐明EBV-miR-BART22促进鼻咽癌细胞转移的作用及分子机制，为治疗鼻咽癌转移提供有效干预靶点。

鼻咽癌病人发生远处转移是导致治疗失败的主要原因。研究表明：EB病毒具有促进鼻咽癌转移的作用，但是，作为首个被发现具有miRNA编码能力的人类病毒，EB病毒编码的miRNA与鼻咽癌转移的关系尚不明确。因此，本项目拟利用临床标本、体内动物模型和体外细胞模型，证实EBV-miR-BART22诱发鼻咽癌细胞转移的作用，阐明EBV-miR-BART22促进鼻咽癌细胞转移的关键信号通路及靶基因。.我们通过研究发现：①EBV-miR-BART22在转移性鼻咽癌组织中表达升高；②EBV-miR-BART22促进鼻咽癌细胞迁移和侵袭；③EBV-miR-BART22诱发鼻咽癌细胞上皮-间充质转化；④动物体内实验证实EBV-miR-BART22促进鼻咽癌细胞转移；⑤EBV-miR-BART22通过激活Wnt/β-catenin信号通路促进鼻咽癌细胞上皮-间充质转化和转移；⑥Wnt信号通路负向调节因子Nemo-like kinase可能是EBV-miR-BART22促进鼻咽癌细胞上皮-间充质转化和转移的靶基因。.本研究重点阐明了EBV-miR-BART22促进鼻咽癌细胞转移的作用及分子机制，为筛选治疗鼻咽癌转移候选干预靶点提供理论依据。