环状RNA circ-EMTI通过调控翻译起始因子eIF4G促进舌鳞癌细胞的上皮间质转化

区域转移是舌鳞癌患者的主要致死因素。近年肿瘤进化研究揭示恶性肿瘤转移并非特异突变决定簇的特殊进程，而是上皮间质转化（EMT）相关信号通路的级联放大输出的结果，其中非编码RNA及其分子调控网络扮演着重要的角色。本研究结合课题组既往非编码RNA研究基础，通过对5组舌鳞癌癌旁组织、原发灶以及转移淋巴结行转录组高通量测序，筛选出调控舌鳞癌侵袭迁移的环状RNA, circ-EMTI；同时生物信息学以及RNA结合蛋白免疫沉淀初步证实circ-EMTI可与翻译起始因子eIF4G结合。后续研究我们将进一步剖析circ-EMTI与eIF4G的分子作用机制以及circ-EMTI/eIF4G复合物对舌鳞癌EMT关键信号通路分子翻译水平的调控作用；并进一步通过体内实验以及临床样本验证其与舌鳞癌转移和预后的关系。因而，本研究将为circRNA参与翻译调控提供新的分子模型，并为临床预测及干预舌鳞癌转移提供潜在靶标。

Regional metastasis is the main cause of death in tongue squamous cell carcinoma(TSCC). In recent years, studies on cancer evolution have revealed that cancer metastasis is not a special process of specific mutations, but rather the result of cascade amplification of epithelial-mesenchymal transition (EMT) -related signaling pathways, in which non-coding RNAs and their associated molecular networks play an important role. Basing on our previous researches of non-coding RNA, we have found circRNA circ-EMTI could regulate invasion and migration of TSCC, by high-throughput transcriptome sequencing of 5 paired specimen that including peritumor tissues, primary and metastatic lymph node foci of tongue squamous cell carcinoma. Meanwhile, we also detected that circ-EMTI could bind to the translation initiation factor eIF4G by bioinformatical analysis and RNA-binding protein immunoprecipitation. Next, we will further to explore the interaction of circ-EMTI and eIF4G as well as the regulatory functions of circ-EMTI / eIF4G complex on the pivotal molecules in EMT-related pathway at the translational level; then to validate their relationship with metastasis and prognosis of tongue squamous cell carcinoma via experiments in vivo and clinical specimens. Therefore, our study will provide a novel mechanism model of circRNA in translational regulation, as well as a potential target for prediction and intervention of TSCC metastasis in clinical setting.