肝癌转移常导致治疗失败，探究其转移机制及新治疗靶点是临床的重大需求。我们预实验结果显示：miR-370-3p可同时负调控Twist1和Snail、抑制肝癌Huh7细胞侵袭和转移，并拮抗IL8促癌作用。另外，IL8下调miR-370-3p表达，提示肝癌可能存在IL8/miR-370-3p/Twist1和Snail通路。本项目拟：①用多个肝癌细胞系，在细胞水平和动物体内实验进一步明确该通路对转移的作用；②在移植肝癌模型中，用纳米载体携带miR-370-3p类似物和多柔吡星，探讨同时抑制转移和增殖是否可改善疗效；③统计分析患者血清IL8、癌组织miR-370-3p、Twist1和Snail表达水平与肝癌转移的临床相关性，建立肝癌转移预测模型并评估其价值。本项目完成将阐明IL8/miR-370-3p/Twist1和Snail通路在肝癌转移中的机制和意义，为肝癌转移的预测或/和治疗提供新思路和靶标。

Metastasis is one of the most fatal causes of therapeutic failure of hepatocellular carcinoma (HCC). Elucidation of the metastasis mechanism and exploration of new targets for HCC therapy are urgently needed. Our previous studies had demonstrated that, miR-370-3p down-regulated Twist1 and Snail, and inhibited Huh7 cells metastasis. Further results showed that interleukin 8 (IL8) up-regulated Twist1 and Snail, and simultaneously down-regulated miR-370-3p in Huh7 cells, indicating a possible pathway that IL8/miR-370-3p/Twist1 and Snail regulates HCC metastasis. In this study, we plan to perform a series experiments to investigate the mechanism and clinical relevance of IL8/miR-370-3p /Twist1 and Snail pathway in HCC by following steps. ① Multi HCC cell lines will be utilized to further confirm the pro-metastasis function of IL8/miR-370-3p/Twist1 and Snail pathway in vitro and in vivo. ② In order to test whether miR-370-3p serve as a therapeutic target to inhibit HCC metastasis, the experiment of in vivo anti-tumor effect using nanoparticles containing miR-370-3p mimic and doxorubicin will be performed in xenografts mice. ③ Data of serum IL8, tumor tissue miR-370-3p, Twist1, and Snail levels in HCC patients will be collected, and correlations between these factors and tumor metastasis will be evaluated. Then, the predictive value of these multi markers and relevance with clinical features will be investigated. The present study will elucidate the mechanism of IL8/miR-370-3p/Twist1 and Snail pathway in promoting HCC metastasis, and the results may provide new prognostic predictors and/or therapeutic targets for HCC.