肿瘤相关巨噬细胞TAM在HCC发生发展中起着重要作用，但其在HCC转移中的作用及机制尚未阐明。我们前期研究发现，TAM中miR-9的甲基化失活参与了TAM介导的HCC转移。结合相关文献推测，TAM中miR-9因甲基化失活致使其靶基因MALAT1调控的TGF-β激活，激活的TGF-β也会诱导MALAT1的表达，促使TAM内TGF-β不断被激活并大量释放，导致肝癌细胞内TGF-β通路及下游相关蛋白的表达参与HCC转移。为证实此假设，我们将分析临床肝癌标本中TAM分布及miR-9、MALAT1、TGF-β的表达与HCC转移的相关性；采用体外TAM和肝癌细胞的共培养，探析miR-9/MALAT1/TGF-β通路对HCC转移的作用及机制；通过肝癌动物模型，证实TAM中miR-9对HCC转移的作用及机制。本课题将有助于深入了解HCC转移的机制，为探索更有效的生物靶向治疗提供新的依据。

Tumor-associated macrophage(TAM) palys an important role in the development of hepatocellular carcinoma, yet its role in HCC metastasis remains uncertain. Our preliminary studies suggest that TAM and miR-9 methylation implicated the progression of HCC metastasis. Based on our preliminary data, we hypothesized that miR-9 is silenced by aberrant promoter methylation in TAM cocultured with HCC cells, then down-regulated the expression of MALAT1 by directly target the 3´-untranslated region. MALAT1 up-regulated the expression of TGF-β and also regulated by TGF-β,then promoted metastasis of HCC cells by aberrant activating TGF-βsignaling pathway. In this application, by in vitro and in vivo experiments, we plan to validate the expression of miR-9、MALAT1 and TGF-βin TAM and analyze the correlation with HCC metastasis. We also investigate how TAM promoted metastasis of HCC cells, particularly the mechanism involving the miR-9/MALAT1/TGF-β pathway. The outcome will help to identify molecular mechanism of HCC metastasis, and therapeutic targets for drug discovery against HCC.