正常肝细胞表达MAT1A，而癌变后表达MAT2A。我们前期发现：敲降MAT1A可通过启动子甲基化激活OPN，而MAT2A通过结合ITGB3启动子介导HCC转移，但MAT1A/MAT2A表达水平的上游调控机制尚未阐明。长链非编码RNA(lncRNA)主导众多肿瘤的发生、侵袭和转移，生信分析显示lncRNA参与调控MAT1A基因的表达。鉴此，本研究拟：1.通过生信和功能分析结合体内外实验，筛选出与MAT1A/MAT2A生物学功能相关的关键lncRNA，并验证其对MAT1A/MAT2A表达的调控作用；2.在体探讨经肝动脉化疗栓塞（TACE）术后HCC缺氧对lncRNA及MAT1A/MAT2A表达的影响；3.深入分析lncRNA通过MAT1A/MAT2A对TACE术后肝细胞癌OPN信号通路的调控机制。本研究将丰富人们对肿瘤血管生成与转移机制的认识，并为确立肝癌靶向治疗新策略提供实验依据。

Normal liver cell expresses MAT1A, which is silenced and MAT2A expression is induced in hepatocellular carcinoma.Previously, we have found that in hepatocellular carcinoma (HCC) downregulation of MAT1A, which augmented osteopontin (OPN) expression through decreasing methylation of the OPN promoter, and MAT2A upregulation, which induced integrin β3 (ITGB3) by binding to ITGB3 promoter.However, the upstream regulation mechanism of MAT1A/MAT2A expression level has not been elucidated. Long non-coding RNAs (long ncRNAs, lncRNA) are closely related to the occurrence, invasion and metastasis of numerous tumors. Bioinformatics analysis showed that lncRNAs participate in regulating the MAT1A gene expression. Thus, the present study plan aims to: 1. Select MAT1A/MAT2A biology functions related key lncRNAs and verify the MAT1A/MAT2A gene expression regulation function by bioinformatics analysis and in vitro and in vivo studies; 2. Investigate the effect of HCC hypoxia on lncRNA and MAT1A/MAT2A after TACE. 3. In-depth analysis of the mechanism of lncRNA regulating the OPN signaling pathway by MAT1A/MAT2A in hepatocellular carcinoma after TACE.The results of this study will enrich understanding of the mechanism of HCC promoting angiogenesis and metastasis, and provide a scientific basis for the establishment of new individualized targeted therapy mode for liver cancer.