肝癌是目前世界上恶性程度最高的肿瘤之一，上皮-间充质转变（EMT）是肝癌转移和恶性演进的重要机制，也是导致患者预后不良的重要原因。临床上仍然缺乏对EMT深入的转录调控机制的认识。目前研究发现一些转录共激活因子可以在超级增强子处发生相分离形成液滴，实现转录过程的区室化反应，激活基因表达。本项目前期发现EMT的重要转录因子Twist1，YY1，与组蛋白乙酰转移酶p300互作，而且Twist1，YY1促进miRNA9的表达。Twist1-YY1-p300在细胞核有聚集成核斑点的特征。因此我们推测Twist1-YY1-p300复合体结合在miRNA9的超级增强子区域发生相分离，极大地促进miRNA9的转录活性和表达，从而进一步诱发肝癌EMT，促进肝癌恶性演进。本研究初步阐释了肝癌细胞中转录因子结合超级增强子发生的相分离，并通过超级增强子的形式促进癌基因的表达，为肝癌的治疗提供了潜在的作用靶点。

Hepatocellular carcinoma (HCC) is one of the most malignant tumors in the world. Epithelial-mesenchymal transition (EMT) is an important mechanism of metastasis and malignant progression of HCC, and also an important cause of poor prognosis of patients. There is still a lack of understanding of the transcriptional regulation mechanism of EMT in clinic. At present, it has been found that some transcriptional co-activators can form phase-separated condensates at the super-enhancer to compartmentalise transcription process and activate gene expression. Twist1, YY1, important transcription factors of EMT, interacted with histone acetyltransferase p300, and promoted the expression of miRNA9. Twist1-YY1-p300 has aggregated nucleation spots in the nucleus. Therefore, we speculate that the Twist1-YY1-p300 complex binds to the super-enhancer of miRNA9, which greatly promotes the transcriptional activity of miRNA 9, thus further induces EMT and promotes the malignant evolution of HCC. This study preliminarily elucidates the phase separation of transcription factors binding to super-enhancers in HCC cells, and promotes the expression of oncogenes by binding super-enhancers. This provided a potential target for the treatment of HCC.