DNMT3A2通过lncRNA-TRERNA1-E-cadherin轴在胃癌侵袭转移中作用机制研究

胃癌是具有高度转移性并对生命造成严重危害的恶性肿瘤。上皮细胞间质转化（EMT）是胃癌发生转移过程中重要事件。本课题组近年研究发现DNMT3A2不仅以DNA甲基化及协同组蛋白甲基化作用沉默E-cadherin而诱导胃癌细胞EMT，且结合了lncRNA-TRERNA1在转录、翻译水平调控E-cadherin表达而促进胃癌细胞转移。本项目拟采用RIP,REMSA结合GST pull-down分析DNMT3A2与TRERNA1结合、结合区段及对E-cadherin表达调控, TRERNA1对EMT-TFs的调控及意义；RIP-RNA-seq分析DNMT3A2结合其他lncRNA 及对EMT-TFs的调控；于细胞模型-动物模型-临床样本层面，深入分析DNMT3A2通过TRERNA1-E-cadherin轴及lncRNA在胃癌侵袭转移中作用机制，为胃癌发生转移过程的表观遗传干预提供理论依据和实验基础。

Gastric cancer is a kind of malignant tumor which is highly invasive and metastatic and it is severely harmful to life. Epithelial-mesenchymal transition (EMT) is an important event in the progress of the metastasis of gastric cancer. Our research recently found that DNMT3A2 not only silenced E-cadherin via DNA methylation together with histone methylation, but also combined with lncRNA-TRERNA1 to regulate the expression of E-cadherin in the transcriptional and translational level, inducing gastric cancer EMT and promoting the invasion and metastasis of gastric cancer. REMSA and GST pull-down were applied to analyze the binding region of DNMT3A2 and lncRNA-TRERNA1 and its regulation of the expression of EMT related molecules, besides, the regulation of EMT-TFs by TRERNA1 was also detected. RNA-seq of DNMT3A2-RIP product was employed to explore other targeted lncRNAs of DNMT3A2 and its regulation of EMT-TFs in the level of cell model -animal model -clinical samples. Deep analysis of mechanism of DNMT3A2 in the invasion and metastasis of gastric cancer via lncRNA-TRERNA1-E-cadherin axis, and provided a theoretical basis and an experimental basis for the epigenetic intervention for the invasion and metastasis of gastric cancer.