Jarid2与LncRNA调控PRC2介导的靶基因组蛋白甲基化在终末期肝病发生发展中的作用

PRC2 was a critical epigenetic modifier，and EZH2 is the core catalyzes component of PRC2. EZH2 can mediate target-gene histone methylation and therefore silence target-gene expression. Recently, EZH2 has been testified to play cardinal roles in occurrence and development of end-stage liver disease. However, it was poorly understood about the target genes and regulators of EZH2. Therefore, we employed ChIP-seq and RNA-seq to identify the target genes of EZH2 in hepatoma carcinoma cell, and use CLIP-seq to identify the long non encoding RNA (LncRNA) combined with EZH2, to determine which LncRNA would be of great significance to recruite EZH2 to the target genes. The enzymatic activity of EZH2 is critical for its functionalty, and recent studies indicated that LncRNAs play a critical role in inhition of enzymatic activity when LncRNAs recruite EZH2 to its target genes. Latest research showed Jarid2 could antagonize the inhition of LncRNA. In our prelimary study, we found Jarid2 could enhance the enzymatic activity of EZH2 and affect prognosis of patients with hepatocellular carcinoma (HCC). Based on these data, we hypothesize that interaction of Jarid2 and LncRNAs regulates the enzymatic activity of EZH2 and promotes occurrence and development of HCC. We will further study the action mechanism and regulation factors of PRC2 in end-stage liver disease. In summary, this project will provide novel targets (e.g. Jarid2, EZH2, LncRNA) for the accurate targeted therapy of HCC.

PRC2是重要的表观遗传学调控因子，其核心元件EZH2可介导靶基因的染色体发生组蛋白甲基化，从而沉默靶基因。近年来发现PRC2在终末期肝病中起着重要作用，但具体靶基因及如何定位尚不清楚。为此，我们建立ChIP-seq和RNA-seq技术在肝癌细胞中筛查EZH2的靶基因，同时采用CLIP-seq技术检测与EZH2结合的长非编码RNA（LncRNA），从中筛查出引导EZH2定位的LncRNA。EZH2的酶活性是影响EZH2调控能力的关键，它会受到LncRNA抑制，最新研究显示Jarid2能拮抗LncRNA的抑制作用，我们前期实验也证实Jarid2能提高EZH2酶活性，并影响肝癌预后。为此我们猜想，Jarid2可能和LncRNA相互作用共同调控PRC2，从而诱发肝癌，这是一条全新的肝癌发病机制。我们拟进一步揭示PRC2在终末期肝病中的作用机制和调控因素，为肝癌精准靶向治疗找到新靶点。

PRC2是重要的表观遗传学调控因子，其核心元件EZH2可介导靶基因的染色体发生组蛋白甲基化，从而沉默靶基因。近年来发现PRC2在肝癌中起着重要作用，但具体靶基因及如何定位尚不清楚。为此，我们建立ChIP-seq和RNA-seq技术在肝癌细胞中筛查EZH2的靶基因，同时采用CLIP-seq技术检测与EZH2结合的长非编码RNA（LncRNA），从中筛查出引导EZH2定位的LncRNA。EZH2的酶活性是影响EZH2调控能力的关键，它会受到LncRNA抑制，最新研究显示Jarid2能拮抗LncRNA的抑制作用，我们前期实验也证实Jarid2能提高EZH2酶活性，并影响肝癌预后。为此我们猜想，Jarid2可能和LncRNA相互作用共同调控PRC2，从而诱发肝癌，这是一条全新的肝癌发病机制。我们拟进一步揭示PRC2在肝癌中的作用机制和调控因素，为肝癌精准靶向治疗找到新靶点。