脂多糖(LPS)是肝癌微环境的重要组成部分，肝癌干细胞是肝癌发生发展的根源，肝癌微环境在肝癌干细胞的干性调控中发挥重要作用。我们前期研究发现LPS可有效促进CD133+肝癌干细胞的干性维持，SIRT1在上述过程中发挥重要作用，但具体机制尚不明确。本课题拟通过体内外实验观察LPS对CD133+肝癌干细胞SIRT1表达的影响及SIRT1对肝癌干细胞干性维持的作用；筛选SIRT1下游介导肝癌干细胞干性维持相关信号通路中的关键作用靶点，研究SIRT1对相关分子乙酰化水平的影响；通过过表达或shRNA调控相关分子表达，阐明SIRT1介导的LPS促进肝癌干细胞干性维持的分子机制；最后利用临床肝癌标本和预后资料，分析LPS促进肝癌干细胞干性维持相关机制中关键分子表达与肝癌患者预后的相关性。本课题有助于加深对肝癌微环境与肝癌干细胞交互作用机制的认识，为肝癌的临床治疗提供新的靶点和理论依据。

Lipopolysaccharide (LPS) is an important component in the tumor environment. Cancer stem cells (CSCs) are involved in the progression of hepatocellular carcinoma (HCC), and tumor environment contributes to stemness maintenance. In previous study, we found that LPS promoted liver cancer stem cell maintenance, and SIRT1 was involved. Howere, the mechanism is not clear. In this study, we will investigate the effect of LPS on SIRT1 expression and the role of SIRT1 in liver cancer stem cell maintenance. Next, we will clarify the related signaling pathway which are activated by SIRT1. And the inhibitor and siRNA technology are used to inhibit the targeted gene in liver cancer stem cells in order to clarify the molecular mechanism of SIRT1 regulate CSCs’ maintenance. Combined with clinical and pathological data, the correlation between the targeted genes and stemness associated genes and the prognosis of patient will be analysised. The results of this study will strengthen the understanding the interaction of tumor environment and cancer stem cell , which will provide a new target and theoretical basis for the HCC clinical therapy.