长非编码RNA(lncRNA)参与调控包括细胞增殖分化在内的许多重要基本生命过程。其中lncRNA HULC在肝癌中高表达并促进肿瘤细胞增殖，然而其具体分子机制还不清楚。我们在前期工作中通过SILAC定量蛋白质组学技术对HULC相互作用蛋白进行了系统性筛查，发现HULC与丙酮酸激酶PKM2存在相互作用。PKM2是调控肿瘤细胞有氧糖酵解的关键分子，同时通过调控基因转录影响肿瘤代谢、增殖和转移。我们推测HULC可能通过直接调控PKM2的聚合影响其酶活性从而作用于肝癌细胞有氧糖酵解代谢过程，同时HULC也可能通过PKM2影响其下游基因的表达进一步影响肿瘤细胞增殖。本项目拟深入探索HULC与PKM2的相互作用与调控机制，进一步阐明HULC调控有氧糖酵解的生理功能和分子调控机制，以及HULC调控PKM2下游基因表达的功能和机制，为解析lncRNA分子在调控肿瘤代谢和增殖中的新功能与相关机理奠定基础。

Increasing reports have revealed that long noncoding RNAs (lncRNAs) play important roles in a large spectrum of biological processes, including cell proliferation and differentiation. LncRNA HULC has been reported to be up-regulated in liver cancer and implicated in the regulation of tumor proliferation. However, the detailed molecular mechanism is still largely unknown. In our preliminary study, a systematic screening of the HULC interacting proteins was conducted by using a SILAC labeling based quantitative proteomics method. The results showed that HULC could bind with pyruvate kinase M2 (PKM2). PKM2 is a key glycolytic regulator. It has also been suggested to translocate to the cell nucleus and activate several transcriptional factors. Thus, we hypothesize that HULC may interact with PKM2 and regulate its enzyme activity to modulate glycolysis; furthermore, HULC may also affect gene transcription through PKM2. To test this hypothesis, we will investigate the interaction between HULC and PKM2 and further explore the mechanism whereby HULC regulates glycolysis and cell proliferation.