NLRP3炎性体是固有免疫领域的重要分子和研究热点，其在肿瘤中的作用尚未阐明。申请者前期在国际上首次发现并报道了NLRP3炎性体在肝癌细胞中表达显著下调，并且其表达水平与肝癌的TNM分期和病理Edmonson分级负相关，提示其表达失调参与了肝癌进程。但是NLRP3炎性体在肝癌细胞中表达失调的机制及其如何参与肝癌进程的机制尚不清楚，本项目中拟对此进行深入探讨。我们首先对能够调控NLRP3炎性体的分子进行了筛选，发现E3连接酶TRIM31在肝癌中显著上调，并且能与NLRP3结合并抑制其表达。结合我们的研究基础和该领域的前沿进展，我们拟在该项目中深入探索TRIM31负向调控NLRP3参与肝癌进程的作用，明确TRIM31调控NLRP3分子的关键结构域，并重点研究TRIM31-NLRP3 -mTOR轴在肝癌中的作用效应和机制。该研究将为阐明肝癌进展的分子机制和对其进行分子水平的靶向逆转奠定基础。

NLRP3 inflammasome is the key molecule and research hot point in innate immunity; however its role in tumor has not yet been clarified. The applicant discovered and reported for the first time the deregulation of NLRP3 inflammasome in hepatocarcinoma cells, and its expression level was negatively correlated with the clinical TNM stages and Edmonson grades, which indicated that its deregulation was involved in HCC progression. However, the molecular mechanism of its deregulation is not known, and the mechanisms involved in its contribution to HCC progression is not clarified. These two key scientific question will be explored in this project. Firstly we screened for the molecules that could regulate NLRP3, and we found that TRIM31, an E3 ligase was significantly upregulated in HCC cells and it could bind with NLRP3 and inhibit its expression. Based on our previous data and the research progression, we proposed to explore the mechanism involved in the negative regulation of NLRP3 by TRIM31, and clarified the key functional structure domain responsible for this negative regulation. We are going to focus on the TRIM31-NLRP3-mTOR axis in the HCC progression and its involved mechanism. This study may provide foundation for the elucidation of the mechanism of HCC progression, and provide basis for its targeted reversion of HCC development.