申请人前期发现了一个在肝细胞癌中表达上调，并发挥促癌作用的新基因，将其命名为lncRNA "HCCL5"。对ChIP-seq数据进行分析发现HepG2中HCCL5的下游存在一个超级增强子。超级增强子是具有转录活性增强子的一个大簇，在功能上能够驱动关键基因的表达。进一步对ChIA-PET数据的分析发现该超级增强子在空间上与HCCL5存在直接相互作用，提示超级增强子对肝细胞癌中的HCCL5存在转录调控。预实验表明HCCL5与转录因子ZEB1相互上调，可能形成正反馈。因此，我们提出科学假说：超级增强子驱动HCCL5与ZEB1形成的正反馈，进而加速肝细胞癌的进程。本项目将从细胞、动物和患者组织三个层面证实该科学设想，这将为进一步了解lncRNA在人肝细胞癌中的生物学功能提供依据，为寻找肝细胞癌的治疗靶点和预后标记物提供新的思路。

We previously discovered a new gene that is up-regulated in hepatocellular carcinoma (HCC) and serves as a key oncogene in HCC, named it lncRNA "HCCL5". Analysis of Chromatin Immunoprecipitation-sequencing (ChIP-seq) data in HepG2 revealed a super-enhancer existed in the downstream of HCCL5. Super-enhancers (SEs) are large clusters of transcriptional enhancers that functionally capable of driving the expression of key genes. Further analysis of the Chromatin Interaction Analysis using Paired End Tag sequencing (ChIA-PET) data revealed that the super-enhancer could interact directly with HCCL5 in physical structure, suggesting that the super-enhancer has transcriptional regulation on expression of HCCL5 in HCC. In addition, our preliminary experiments showed that there likely existed a positive feedback in the up-regulation of HCCL5 and ZEB1. Therefore, we propose a scientific hypothesis that the super-enhancer may drive the formation of a positive feedback regulation between HCCL5 and ZEB1, thereby accelerating the progression of hepatocellular carcinoma. This study will confirm the scientific hypothesis from the aspects of cell, animal and patients’ sample, and will provide a basis for further understanding of the biological function of lncRNA in human hepatocellular carcinoma and afford a new thought for finding therapeutic targets and prognostic biomarkers of hepatocellular carcinoma patients.