葡萄糖供应不足诱发的能量应激是肿瘤发生的重要标志。能量应激条件下，肿瘤细胞以高水平糖酵解作为供能方式。本项目前期发现：能量应激下LncRNA HOTTIP高表达；HOTTIP促进细胞增殖，且依赖于糖酵解过程；HOTTIP与转录因子c-Myc直接结合；HOTTIP在胃癌组织中高表达，并与不良预后有关。LncRNA参与调节多种生物过程，但是否通过调控糖酵解适应能量应激，参与胃癌发生和发展还有待研究。根据预实验结果，我们提出假说：能量应激诱导的HOTTIP可能通过结合c-Myc，促进其在靶基因启动子区的富集，反式激活下游糖酵解基因的表达，促进糖酵解过程和胃癌恶性进展。本项目拟通过细胞-动物-临床不同层面的系统研究，探讨能量应激条件下HOTTIP通过c-Myc介导的糖酵解过程，促进胃癌恶性进展的作用和分子机制；揭示HOTTIP的临床意义，最终为以糖代谢为基础的胃癌靶向治疗提供实验依据。

The energy stress induced by insufficient glucose supply is an important hallmark of tumorigenesis. Under the condition of energy stress, the high level of glycolysis was maintained as the energy supply in tumor cells. Our previous study had showed that: lncRNA HOTTIP was induced by energy stress. HOTTIP promoted cell proliferation which was depended on glycolysis. HOTTIP directly combined with the transcription factor c-Myc. HOTTIP was highly expressed in gastric cancer tissues, and might be associated with poor prognosis of patients. LncRNA is involved in the regulation of a variety of biological processes, but it is not clear whether lncRNA regulate glycolysis and promote gastric tumorigenesis and development under energy stress. Based on the previous results, we propose a hypothesis: HOTTIP induced by energy stress may promote the recruitment of c-Myc in the promoter regions of target genes, activates the expression of key genes of glycolysis in trans, and promotes the malignant progression of gastric cancer. Through cancer cell, mice model and clinical studies, this subject is to elucidate the role and molecular mechanism of HOTTIP in promoting malignant progression of gastric cancer through c-Myc mediated glycolysis under energy stress, to reveal the clinical significance of HOTTIP and finally provide experimental basis for metabolism-based targeted therapy for gastric cancer.