肝癌复发转移的分子调控机制是目前研究的重点。我们前期研究发现Mus81基因与肝癌临床病理特征及预后密切相关并可调控肝癌的增殖凋亡及化疗敏感性，预实验已证实Mus81基因敲减可明显抑制肝癌细胞的侵袭迁移，且采用基因芯片发现Mus81敲减导致肝癌细胞中685个基因差异表达，并以生物信息学方法分析肿瘤基因组图谱（TCGA）大数据从中筛选出8个候选Mus81下游调控基因。因此，我们推测Mus81可能是促进肝癌侵袭转移的关键基因，但其作用机制目前尚不清楚。为此，本项目拟采用功能缺失/获得及回复实验、裸鼠肝癌原位转移模型和活体成像技术进一步验证Mus81在肝癌侵袭转移中的作用，进而以高内涵筛选及qPCR芯片等高通量技术筛选Mus81调控肝癌侵袭转移的分子信号通路，并在肝癌标本、细胞系及裸鼠瘤体中予以验证。本项目将阐明Mus81促进肝癌侵袭转移的分子机制，并有望为肝癌复发转移的干预提供一个新的治疗靶点。

The molecular mechanism underling the recurrence and metastasis of hepatocellular carcinoma (HCC) is a key issue in the research of this malignancy. In the previous studies, we have found the expression of Mus81 is closely related to the clinicopathological features and prognosis of HCC and is also involved in the regulation of proliferation, apoptosis and chemosensitivity of HCC. Our preliminary experiments have indicated that Mus81 knockdown by lentivirus-mediated short interfering RNA (siRNA) could obviously suppress the invasion and migration of HCC cell line. The results of cDNA microarray have shown that 685 genes differently expressed in Mus81 depleted HCC cell line, of which 8 genes were screened as Mus81 downstream regulators by analyzing the big data from The Cancer Genome Atlas (TCGA) with the bioinformatics methods. Therefore, we presumed that Mus81 might be a critical gene faciliating the invasion and metastasis of HCC, while the molecular mechanisms underlying this faciliation are still unknown. Thus, we plan to further explore the implication of Mus81 on the invasion and metastasis of HCC by loss- and gain-of-function studies and add-back rescue experiment, nude mice HCC metastasis model and live animal imaging technology. Meanwhile, we plan to screen the downstream target genes and the corresponding signaling pathway of Mus81 by high throughput screen technology such as high content screen and qPCR array and verify them in HCC tissue samples, cell lines and nude mice xenocraft tumors. The present proposal aims to elucidate the molecular mechanism of Mus81 in faciliating invasion and metastasis of HCC and to provide a novel therapeutic target for the intervention to the recurrence and metastasis of HCC.