核受体Nur77（也被称为TR3）具有复杂多样的生物学功能，可通过蛋白质相互作用或直接诱导下游基因表达参与肿瘤发生发展以及机体代谢稳态的调控，但Nur77是否调控lncRNA来发挥作用还不清楚。预实验中，我们发现Nur77的转录激活活性对其抑制肝癌细胞生长至关重要。通过lncRNA芯片分析，我们筛选到一个表达受Nur77调控的新的lncRNA—NILA1，它在肝癌中的表达与Nur77呈正相关，并且显著低于癌旁组织。进一步研究发现NILA1可与两个糖酵解限速酶结合，并抑制肝癌细胞糖酵解和肝癌细胞生长。本项目将据此进一步研究Nur77调控NILA1表达的作用与机制；分析NILA1调控糖酵解的机制及其对肝癌细胞生长的抑制作用；探讨Nur77通过调控NILA1对肝癌发生发展的影响。通过研究，有望阐明Nur77及NILA1对肝癌细胞葡萄糖代谢重编程的调控作用，为肝癌的防治提供新思路与新靶点。

Nuclear receptor Nur77 (also known as TR3) possesses diverse biological functions, and contributes to the regulation of tumor development and metabolic homeostasis through protein-protein interaction or inducing downstream target genes’ expression. However, whether Nur77 regulates the expressions and functions of lncRNA is still unknown. In our preliminary experiments, we found that the transcriptional activity of Nur77 is required for its inhibitory effect on hepatocellular carcinoma (HCC) cell proliferation. Through an lncRNA microarray analysis, we found a new Nur77-regulated lncRNA named NILA1, which is lower expressed in HCC tissues than in para-carcinoma tissues, and the expression of NILA1 in HCC samples is positive correlated with Nur77. Further studies showed that NILA1 not only bound to two rate-limiting enzymes in glycolysis, but also inhibited glycolysis and HCC development. In this project, we will further study the regulatory effect of Nur77 on NILA1 expression, the underlining mechanism of NILA1 on glycolysis regulation and the inhibitory function of Nur77 and NILA1 on HCC development. Together, our study will not only clarify the regulatory role of Nur77 and NILA1 on the glucose metabolic reprogramming, but also provide new ideas and potential targets for HCC therapy.