我们前期研究报道，肿瘤包绕型血管（VETC）能促进肝癌转移，可作为独立的预后指标；并证明Angiopoietin-2 (Ang-2)在VETC+肝癌中显著增高，是介导VETC形成的关键分子【Hepatology, 2015】。然而Ang-2表达的调控机制及其临床意义尚不清楚。已知转录因子和miRNA是调控基因表达的重要分子，于是我们在VETC-/+肝癌样本中进行高通量筛选，鉴定了多个表达差异的转录因子和miRNA。以此为基础，本项目拟结合细胞、小鼠模型和人肝癌组织标本，鉴定调控Ang-2表达的转录因子和miRNA，并揭示其分子机制及对VETC形成和转移的作用；利用超声微泡高效且特异地向小鼠移植瘤中导入Ang-2表达调控分子，探讨选择性治疗恶性程度更高的VETC+肝癌的可行性。所得结果不仅有助于更全面地认识肝癌血管形成的调控机制，还为肝癌治疗提供新的分子靶点和策略。

We have demonstrated that vessels that encapsulated tumor clusters (VETCs) facilitate metastasis of hepatoma carcinoma (HCC) and may serve as an indicator of prognosis. Furthermore, angiopoietin-2 (Ang-2) was found significantly upregulated in VETC+ HCCs and identified as a prerequisite for VETC formation [Hepatology, 2015]. However, the regulatory mechanism of ectopic Ang-2 expression and its clinical significance remain unclear in HCC. It’s known that transcription factors and miRNAs are key regulators of gene expression. Based on microarray and bioinformatic analyses, we have identified a cohort of transcription factors and miRNAs that were differentially expressed in HCC tissues with or without VETC. With these findings, we will further investigate the regulatory mechanisms of Ang-2 expression and VETC formation that were mediated by target transcription factor and miRNA. We will also evaluate the possibility of selective therapy against VETC+ HCC by using ultrasound-guided microbubble to intervene the expression of these VETC regulators. The results obtained not only contribute to a more comprehensive understanding about HCC angiogenesis, but also provide novel targets and concepts for anti-angiogenesis therapy.