术后复发、转移是影响肝癌患者长期预后不佳的主要原因，然而其具体分子机制尚不十分明确。课题组前期研究发现 GOLM1是调控肝癌侵袭、转移的重要分子，质谱分析及IP技术提示GOLM1与TLR9存在相互作用，且在基因水平可影响TLR9。组织芯片提示TLR9在肝癌组织中高表达，且与肝癌患者预后差密切相关。另外，体外实验发现GOLM1高表达时细胞自噬高水平，敲减GOLM1后TLR9表达量下降，细胞自噬水平降低。据此提出“GOLM1通过与TLR9相互作用，调控自噬相关基因表达，上调自噬活性，从而增加肝癌细胞侵袭转移能力”的假设。进一步，我们将围绕GOLM1/TLR9调控机制展开研究，采用Co-IP、高通量质谱分析及芯片技术等方法明确GOLM1/TLR9功能通路如何调节自噬水平对肝癌细胞恶性潜能的影响。探索针对该通路进行干预是否抑制肝癌的生长和侵袭转移。

Recurrence and metastasis are the main reasons that affect the long-term prognosis of HCC patients, but its molecular mechanism is not well understood. Our previous study found that GOLM1 was an important molecule to promote invasion and metastasis of HCC. Mass spectrometric analysis and IP technique indicated that GOLM1 may interact with TLR9 and could regulate TLR9 at the gene level. Besides, our data suggested that TLR9 was highly expressed in HCC tissues and was closely related to the poor prognosis of HCC patients. It was found in vitro that high level of autophagy was in concordance with high expression of GOLM1 and autophagy was decreased as well as level of TLR9 expression after knockout of GOLM1. According to our previous outcomes, we raise a presumption that "GOLM1 may interact with TLR9 to regulate the expression of autophagy related genes and enhance autophagy activity , thus promote the invasion and metastasis of liver cancer cells. In this project, we will focus on how the GOLM1 / TLR9 regulate the level of autophagy to affect the malignant potential of liver cancer cells by using experimental technique such as Co-IP , high - throughput mass spectrometry and chip technology.