VEGFA/VEGFR2信号活化构成胃癌血管新生的重要分子病理基础。我们发现血管新生相关miR-296/298簇miRNA：miR-296-5p在胃癌中上调，转录因子PLAG1可促进miR-296/298簇表达，且miR-296/298簇可靶向抑制多种蛋白苏素化修饰基因，上调miR-296/298簇可能抑制PLAG1苏素化修饰而增强其转录活性。课题组亦验证了既往结论：VEGFA受PLAG1转录，miR-296-5p靶向抑制VEGFR2降解蛋白HGS从而维持VEGFR2表达，干预PLAG1或miR-296/298簇，可影响VEGFA/VEGFR2表达及体外血管新生。由此，我们提出假说：PLAG1与miR-296/298簇之间存在反馈通路，导致VEGFA/VEGFR2信号活化促进胃癌血管新生。我们拟结合临床样本检测，细胞、分子机制研究及体内外效能验证，阐明该假说，以利胃癌抗血管新生治疗。

Sustained activation of VEGFA/VEGFR2 signaling constitutes an important molecular pathological basis of angiogenesis in gastric cancer. Our previous research found that angiogenesis related miR-296/298 cluster miRNA:miR-296-5p was upregulated in gastric cancer, and transcription factor PLAG1 could promote miR-296/298 cluster expression, and various sumoylation related genes inhibiting the transcriptional activity of PLAG1 were direct targets of miR-296/298 cluster miRNAs. Overexpression of miR-296/298 cluster could enhance the transcriptional activity of PLAG1 possibly via inhibiting its sumoylation. Meanwhile, we verified the previous conclusion that VEGFA is upregulated by PLAG1 and HGS degradating VEGFR2 is targeted by miR-296-5p. Alterations of VEGFA/VEGFR2 expression and in vitro angiogenesis were observed after the intervention of PLAG1 or miR-296/298 cluster. So we put forward the hypothesis that there was a feedback loop between PLAG1 and miR-296/298 cluster, which sustained VEGFA/VEGFR2 signaling, promoting angiogenesis in gastric cancer. We will elucidate our hypothesis based on clinical samples detection, molecular mechanism exploration and efficacy validation in vitro and in vivo. This study will enrich the molecular mechanism of gastric cancer angiogenesis, and provide valuable basic research information for antiangiogenic therapy in gastric cancer.