转移是肝癌致死的根本原因，目前缺乏特异性的治疗靶点。长链非编码RNA（lncRNA）在肿瘤转移中发挥重要作用，寻找调控肝癌转移的关键lncRNA，阐明其功能及分子机制，具有重要的临床意义。前期我们报道揭示甲基转移酶SMYD3能促进肝癌转移《Oncogene》。近期，我们进行RNA测序分析发现lncRNA-HCG18在SMYD3高表达的肝癌样品中显著上调。进一步我们研究发现HCG18可以①结合SMYD3，增强其甲基转移酶活性，上调MMP2转录水平，导致细胞基质降解，促进肿瘤细胞的侵袭；②结合去泛素化酶USP15，促进IκB-α的泛素化降解，激活NF-κB信号通路，上调VEGFA与BCL2的表达，进而诱导血管新生并抵抗失巢凋亡；最终多层面促进肝癌转移。然而，其中的具体机制仍需进一步阐明。因此，我们将更深层次探讨HCG18诱导肝癌转移的详细分子机制，并结合临床，明确其在肝癌诊治中的应用价值。

Metastasis is the fundamental cause of death for hepatocellular carcinoma. However, there is no specific therapeutic target. Long non-coding RNA (lncRNA) plays an important role in tumor metastasis. It is of great value to indentify the key lncRNA and elucidate the mechanism in metastasis. Previously, we reported that methyltransferase SMYD3 promotes hepatocellular carcinoma metastasis (Oncogene). Recently, we found that lncRNA-HCG18 is remarkedly upregulated in the hepatocellular carcinoma samples with SMYD3 highly expressed.Furthmore, we found that HCG18 can interact with SMYD3 and enhance its enzyme activity, and then upregulate the expression of MMP2, lead to cell matrix degradation, and promote the invasion of tumor cells. We then demonstrated that HCG18 could also interact with the deubiquitinase USP15 and enhance the ubiquitin-related degradation of IκB-α, promote the nuclear transposition of P65, and increase the transcriptional activity of NF-κB, lead to the up-regulation of VEGFA and Bcl-2, thereby induce angiogenesis and anoikis resistance. Thus, our results show an important role of HCG18 in metastasis. In this project, we aim to explore the biological roles and the detailed underlying mechanisms in which HCG18 promotes metastasis, which might shed light on the molecular mechanism in the tumor development and progression in hepatocellular carcinoma, and then to provide new therapeutic target for hepatocellular carcinoma.