大量的研究表明，肿瘤细胞的Warburg效应对于肿瘤的发生发展至关重要。肿瘤细胞的Warburg效应被认为是由多种机制共同作用形成，其中一个重要的机制认为Warburg效应是肿瘤细胞对其所处低氧微环境的一种适应，然而其具体的分子基础仍不明确，特别是关于长片断非编码RNA是否以及如何调控低氧微环境下肿瘤细胞的Warburg效应并不清楚。本项目以此为研究切入点，我们前期的研究结果暗示：低氧条件下，被低氧诱导因子HIF-1α激活表达的lncRNA-HILR1可能通过结合HIF-1α并抑制其降解，从而形成一个正反馈循环，最终促进肿瘤细胞的Warburg效应。本项目将在已有的工作基础上，深入研究lncRNA-HILR1调控低氧条件下肿瘤细胞Warburg效应的作用及机制；同时也将研究其在肿瘤发生发展中的作用。这将有助于人们更加深入地理解肿瘤细胞的Warburg效应，并可能为肿瘤治疗提供新的潜在靶点。

It has been recognized for a long time that the metabolism of cancer cells is significantly different from that of their normal cell counterparts. Cancer cells exhibit a unique metabolism referred to as the Warburg effect characterized by enhanced glycolysis and reduced oxidative phosphorylation even in the presence of oxygen. The Warburg effect allows cancer cells to metabolize large quantities of glucose in order to generate the biomass required for the rapid cell proliferation, thereby facilitating tumorigenesis. The underlying biochemical and molecular mechanisms of the Warburg effect are multiple, yet one of the most recognized mechanisms is the adaptive response to the unique tumor hypoxic microenvironment. It has been known that under hypoxic conditions, activation of hypoxia inducible factor 1 (HIF-1) contributes to the Warburg effect through co-ordinated upregulation of glycolytic enzymes and downregulation of mitochondrial oxidative phosphorylation. However, whether long non-coding RNA (lncRNA) is involved in the contribution of hypoxia/HIF-1 to the Warburg effect still remains unknown. Our research aims to address this issue. Our preliminary data suggest that hypoxia/HIF-1a-induced lncRNA-HILR1 (Hypoxia-inducible long non-coding RNA 1) could in turn interact with HIF-1a and inhibit its degradation, thus forming a positive feedback loop to promote the Warburg effect. In this study, we will further investigate the molecular mechanism whereby lncRNA-HILR1 regulates the Warburg effect under hypoxic conditions. We will also evaluate the possible role of lncRNA-HILR1 in cancer initiation and progression. This study will generate novel insights into the mechanisms of the Warburg effect. This may also implicate lncRNA-HILR1 as a novel potential therapeutic target for the treatment of cancer.