血管新生是肝癌发展关键因素之一。Pokemon作为转录抑制因子在肝癌血管新生中的作用及机制尚未明确。本课题前期研究发现，基因沉默Pokemon明显抑制血管内皮细胞成管能力，并显著降低移植瘤血管密度；也发现Pokemon上调肝癌细胞中HIF-1α蛋白水平，但不影响HIF-1α mRNA水平，而是抑制了促进HIF-1α降解的蛋白pVHL mRNA转录。Luciferase、EMSA和CH-IP证实Pokemon抑制pVHL启动子转录活性。由此我们推测，Pokemon通过抑制pVHL转录，影响HIF-1α稳定性，促进肝癌血管生成。因此本课题将：进一步明确Pokemon调控pVHL转录，抑制HIF-1α降解；明确Pokemon通过HIF-1α在体内外促进肝癌血管生成；肝癌标本验证Pokemon与HIF-1α表达呈正相关及与肝癌患者临床特征关系。从而阐明Pokemon促进肝癌血管生成的分子调控机制。

Angiogenesis is one of the key factors in the development of hepatocellular carcinoma (HCC). Pokemon is a transcription factor with proto-oncogene activity, play an important role in the process of HCC. However, its function and mechanism during angiogenesis in HCC is not yet explored. Our preliminary data demonstrated that knocked-down of Pokemon significantly inhibits the vascular endothelial cells to form blood vessels in vitro. The vascular density in xenografts tumor which Pokemon knocked-down HCC cells was reduced compared with the control. We found that Pokemon upregulated the protein expression of HIF-1α in HCC cells. However, it did not affect the mRNA expression of HIF-1a , instead of inhibiting the mRNA expression of pVHL which promotes the ubiquitination and degradation of HIF-1a. EMSA, CHIP and Luciferase assay showed that Pokemon bound to the promoter of pVHL and regulated the transcriptional activity of pVHL. Therefore, we speculated that Pokemon inhibits transcription of pVHL, inhibits the degradation of HIF-1a and enhances the angiogenesis in HCC. Thus, in this study, we will further define that Pokemon regulates the transcription of pVHL, inhibits the HIF-1α degradation to promote the angiogenesis in HCC both in vitro and in vivo. To confirm the expression of Pokemon and HIF-1α was positively correlated in HCC tissue and analyze the relationship between its expression and clinical characteristics. We aimed to address the regulation mechanism of Pokemon to promote angiogenesis in HCC development.