铁代谢异常与肝癌紧密相关。我们和前人报道了肝铁过负荷不仅下调miR122诱导肝癌发生（Blood，2017），亦可促进肝癌增殖。但铁与肝癌转移是否有关尚不明确。我们的前期研究首次发现铁缺乏在免疫缺陷小鼠中促进肝癌转移，并增强转移相关miR210表达；此外，敲低miR210可显著下降铁缺乏的作用。因此推测铁缺乏导致miR210上调促进肝癌转移，此过程独立于肿瘤免疫之外。本项目拟首先改造腺相关病毒载体的嗜肝性，使其在铁缺乏状态下能体内靶向转导人肝癌移植瘤，从而排除肿瘤着床、生长等非转移因素的干扰。其次，深入探索铁缺乏时miR210上游转录因子和下游靶基因等信号通路的变化及功能。再分析临床肝癌样本中铁含量、癌转移预后、miR210及其靶基因表达四者间的相关性。最终阐明铁缺乏促肝癌转移的分子机制。为避免单纯补铁可能引起肝铁过负荷，本项目将通过精准调控分子靶点开发抑制肝癌转移的新策略。

To date, metastasis is still the top reason responsible for the mortality of hepatocellular carcinoma (HCC) patients. It is urgent to reveal new molecular mechanisms and potential drug targets. On the other hand, iron is essential for tumor growth. However, few reports focused on how iron metabolism regulate microRNA expression in tumors. Our early publications documented that iron abnormal reduces the miR-122 pathway and consequently induces HCC initiation (Blood.2017;130(8):1041-51). In addition, our preliminary studies indicated that iron-deficiency significantly increased the metastasis of HCC in various models. Interestingly, iron-deficiency enhanced the HCC metastasis in an immune-deficient mouse model. Further microarray studies demonstrated that at least 6 metastasis-related miRNAs were upregulated upon iron-deficiency. Based on these findings, we will: 1) further prove that iron-deficiency induced HCC metastasis is irrelevant to the tumor immuno-microenvironment. 2) investigate the underlying mechanism how iron-deficiency regulates metastasis-related miRNA in human HCC cells. 3) study the regulation of downstream protein targets under the condition of iron-deficiency and discover the potential new drug targets. Should our project successfully conducted, new ideas will be provided to prevent HCC metastasis.