MAT是一类由MAT1A和MAT2A催化S-腺苷蛋胺酸合成的转移酶，正常肝细胞表达MAT1A基因，而癌变后则表达MAT2A基因；骨桥蛋白(OPN)是一种分泌型磷酸化糖蛋白，通过与其受体整合素和CD44相互作用，介导肿瘤侵袭转移的多个过程。我们前期发现：过表达MAT1A并敲低MAT2A的表达能明显抑制肝细胞癌(HCC)的促血管生成能力，敲低OPN可模拟过表达MAT1A并敲低MAT2A抑制HCC迁移侵袭的功能表型，但其分子机制尚未阐明。鉴此，本研究拟：1. 验证MAT1A/MAT2A协同调控HCC血管生成与转移的效应转录分子。2.明确HCC中MAT1A/MAT2A与OPN信号通路上下游因子之间的相互作用。3.揭示MAT1A/MAT2A对肝细胞癌TACE术后OPN信号通路的调控机制。本研究将深化人们对HCC血管新生与转移分子机制的认识，并为克服TACE术后HCC复发转移的靶向治疗提供新的思路。

Two genes (MAT1A and MAT2A) encode for the essential enzyme methionine adenosyltransferase (MAT), which catalyzes the biosynthesis of S-adenosylmethionine (SAMe).Normal liver cell expresses MAT1A, which is silenced and MAT2A expression is induced in hepatocellular carcinoma.Osteopontin (OPN) is a secreted, integrin-binding protein,that plays an important role in tumor invasion, migration and progression in several cancer types through binding certain CD44 variants and integrin receptors. Our previous studies showed that overexpressed MAT1A and knockdown MAT2A expression could inhibit growth of HCC and the process of angiogenesis, and knockdown OPN could simulate overexpressed MAT1A and knockdown MAT2A expression and inhibit the invasiveness and metastasis of hepatocellular carcinoma (HCC).However,the underlying molecular mechanisms remain to be elucidated. Thus, the present study plan aims to 1.To verify theexpression ofeffectors ofangiogenesis andmetastasis coordinately regulated by MAT1A/MAT2A in HCC. 2.To clarify the effect mechanismof OPN signaling pathwaysassociated with MAT1A and MAT2A in HCC. 3. To explore the effect mechanism of OPN signaling pathways regulated by MAT1A and MAT2A in HCC after TACE. The results of this study will provide an in-depth understanding of the molecularmechanism of angiogenesis and metastasis and the scientific basis for identifying novel individual target therapy mode in HCC patients with recurrence and metastasis after TACE.