肝癌作为高发病率和高死亡率的肿瘤，在全球，尤其是我国，是沉重的健康负担。肝癌复发和转移是导致预后差的主要原因。在前期工作中，我们发现SWI/SNF复合物中的一个成员ARID2在肝癌，尤其是门静脉癌栓中的表达下调，ARID2显著抑制肝癌转移，而ARID2 knockout则促进了肝癌细胞的转移，并上调了脂质摄取和合成基因的表达，增加了肝癌细胞中的脂滴累积。基于这些发现，我们提出了一个科学假设：ARID2通过调控脂代谢影响了肝癌的转移。在本项目中，我们将结合临床肝癌样本、细胞和动物模型，1.探索ARID2响应脂质信号，调控脂代谢和转移的机制；2.阐述ARID2对脂代谢的调控在肝癌转移中的作用；3.针对ARID2下游影响转移的脂代谢靶分子探索肝癌转移的治疗策略。本项目将不仅揭示ARID2新的生物学功能，还将为肝癌转移的治疗提供新的靶点和思路。

Due to the high incidence and mortality, hepatocellular carcinoma (HCC) remains a major health burden globally, especially in China. Recurrence and metastasis are the major obstacle to improving the poor prognosis of HCC. In the preliminary study, we found that the expression of ARID2, a component of SWI/SNF complex, was decreased in HCC,especially in portal vein tumor thrombus. ARID2 suppressed HCC metastasis, while knockout of ARID2 promoted metastasis of HCC cells, upregulated the expression of the genes involved in lipid uptake and synthesis, and increased lipid droplet accumulation in hepatocytes and HCC cells. Therefore we hypothesize that ARID2 might influence HCC metastasis via regulation of lipid metabolism. In this program, we will investigate the mechanism underlying the regulation of lipid metabolism and metastasis by ARID2 in response to the extracellular lipid signals, clarify the role of ARID2-regulated lipid metabolism in HCC metastasis, and explore the therapeutic potential of the strategy targeting ARID2-regulated lipid metabolism. This work will not only reveal the novel function of ARID2, but also provide new targets and ideas to facilitate the treatment of HCC metastasis.