胃癌是我国最常见的恶性肿瘤，如何抑制其侵袭转移是亟待解决的难题。LINC00473是本课题组通过lncRNAs表达谱芯片筛选获得的、显著高表达于胃癌组织的lncRNA，其对胃癌的调控作用迄今未见研究报道。我们发现干扰LINC00473表达可显著抑制胃癌细胞的迁移、侵袭水平；转录组高通量测序提示，自噬抑制基因XIAP可能作为其靶基因，参与抑制细胞自噬、促进侵袭转移；生物信息学分析显示LINC00473可能与HuR结合从转录后水平调控XIAP mRNA的稳定性，但确切的机制尚待研究。因此，我们提出LINC00473通过结合HuR调控靶基因XIAP的稳定性，抑制肿瘤细胞自噬，促进胃癌侵袭转移的新假设。本课题拟以临床样本验证相关分子表达规律、以细胞及动物模型验证关键分子的调控机制，初步阐明LINC00473通过XIAP调控胃癌侵袭转移的分子机制，旨在为胃癌的预后判断和治疗提供新的分子靶标。

Gastric cancer is the most common malignant tumor in China. Inhibition of invasion and metastasis is important in the therapy of gastric cancer. Using lncRNAs expression profile microarray, we found that LINC00473 was highly expressed in gastric cancer compared to adjacent normal tissue. So far, its regulation mechanisms in the development of gastric cancer has not been discussed. In our pre-experiments, LINC00473 was highly expressed in not only gastric cancer tissue but also gastric cancer cell lines. Meanwhile, down-regulated expression of LINC00473 could significantly inhibit migration and invasion in gastric cancer cells. And high-throughput sequencing on transcriptome results showed that autophagy-related gene XIAP could be one target gene of LINC00473, thereby influencing autophagy in tumor cells to regulate invasion and metastasis. Bioinformatics analysis showed that LINC00473 could link to a RNA-binding protein HuR, subsequently affecting the stability of mRNAs of target gene. But the exact mechanism is not clear. We hypothesized that LINC00473 regulated the stability of target gene XIAP by combining with HuR. Then autophagy was inhibited so that invasion and metastasis of gastric cancer were promoted. In this project, we would further investigate the relationship of LINC00473 and the development of gastric cancer through clinical, cell and animal studies, which mainly focus in the biological functions of LINC00473 and its possible down-stream regulators HuR and XIAP. It would provide detail mechanisms of LINC00473 in gastric cancer, and provide novel sights of lncRNAs and possible therapy targets for gastric cancer.