侵袭和转移是胃癌的重要特征，涉及表观遗传学改变。我们前期工作结合TCGA数据库分析发现在胃癌中miR-338-3p低表达，DNMT3A高表达，两者呈显著负相关，且DNA甲基化抑制剂5’-Aza-dC处理胃癌细胞引起miR-338-3p表达上调；过表达miR-338-3p可显著抑制胃癌细胞的迁移，生物信息学预测其靶向HHAT和Rab14，后二者与肿瘤侵袭转移密切相关，提示DNMT3A表观调控miR-338-3p的表达并通过HHAT和Rab14双靶点影响胃癌侵袭转移。本研究拟应用免疫组化、Western Blot等方法研究DNMT3A─miR-338-3p─HHAT/Rab14轴与胃癌患者的临床相关性；CHIP、qRT-PCR、报告基因、荷瘤小鼠模型等方法在细胞和动物水平系统分析该轴在胃癌侵袭转移中的作用机制。为阐明miR-338-3p在胃癌侵袭转移中的失调机制及寻找潜在治疗靶点提供新的认识。

The epigenetic changes are involved in the invasion and metastasis which are significant features of gastric cancer. Our previous study found that miR-338-3p is decreased and DNMT3A is up regulated together with TCGA database analysis, the negtive relationship was observed between miR-338-3p and DNMT3A in gastric cancers, and the expression of miR-338-3p was increased in gastric cancer cells treaed with 5'-Aza-dC.Overexpression of miR-338-3p can markedly inhibit the migration of gastric cancer cells. The target relationship between miR-338-3p and metastasis-associated HHAT/Rab14 is predicted using bioinformatics. Taken together, we propose that DNMT3A epigeneticly regulates the expression of miR-338-3p to inhibit invasion and migration through co-targeting HHAT and Rab14 in gastric cancer cells. In this study, we will apply immunohistochemistry and western blot to evaluate the clinical significance between gastric cancer patients and DNMT3A - miR-338-3p - HHAT/Rab14 axis. Futhermore, CHIP, qRT-PCR and reporter gene analysis are applied to analyze the effects of DNMT3A - miR-338-3p - HHAT/Rab14 axis on mechanism of invasion and metastasis of gastric cancer. Finally, tumor-bearing mouse model will be performed. Therefore, our research will provide new understanding to elucidate the mechanism of dysregulation of miR-338-3p with the invasion and metastasis of gastric cancer and potential clinical targeted therapy.