转移是肿瘤致死的最主要原因，寻找其关键的调控长链非编码RNA（lncRNA），阐明其功能及分子机制，对晚期恶性肿瘤的诊治具有重要意义。近期，我们筛选到在淋巴结转移性食管癌中表达最显著上调的lncRNA-CASC8。进一步发现：① CASC8能够与NF-κB转录因子复合体p65/p50相结合，增强其转录活性；② CASC8上调MMP9、VEGF-C和CCR7等基因，增强食管癌细胞的迁移和侵袭能力，并诱导淋巴管新生、促进肿瘤淋巴结转移；③ 更为重要的是，CASC8与RNA转运蛋白HNRNPA2B1结合，并被组装进肿瘤外泌体中、活化成纤维细胞，激活其细胞内的NF-κB通路而上调多种炎症因子的表达，从而诱导远处器官炎症微环境形成并诱发肿瘤转移。本项目将承前启后，利用多种技术和方法深层次解析CASC8多层面诱导食管鳞癌转移的分子机制，并结合临床数据分析，探讨CASC8在食管鳞癌临床诊治中的意义。

Metastasis is the most prominent factor for cancer-induced death. Identifying the key long non-coding RNA and elucidating the mechanism in metastasis would be of great value for early diagnosis and targeted therapy. Recently, using the RNA sequencing method, we found that CASC8 is one of the most significantly upregulated lncRNA in esophageal cancer tissues with lymph node metastasis. Furthermore, the RNA and protein immunoprecipitation assays revealed that CASC8 interacted with p65/p50 complex. We then demonstrated that CASC8 increased the transcriptional activity of NF-κB, and upregulated multiple genes including MMP9, VEGFC and CCR7, leading to lymph node metastasis in vivo. Surprisingly, we observed that CASC8 interacted with RNA transporting protein HNRNPA2B1, and was incorporated into exosomes. CASC8 was then able to be transmitted into fibroblast cells, and activated NF-κB signaling in fibroblast to induce cytokines expression. Moreover, CASC8 created inflammatory micro-environment in lymph node and lung tissues, facilitating tumor colonization and growth in distant metastasis sites. Hence, in the current project, we aim to explore the biological roles and underlying mechanisms in which CASC8 promotes ESCC metastasis via exosomes and NF-κB activation, which might provide new biomarkers and targets for the diagnosis and treatment of cancer.