C/EBPβ/AOC4P/LIN28B/IL-6正反馈环路调控STAT3促进胃癌增殖侵袭的机制研究

长链非编码RNA（lncRNA）在胃癌发生发展中发挥了重要作用。AOC4P是我们前期筛选并率先报道的与胃癌相关的较特异lncRNA，具有胃癌筛查诊断的转化应用价值，但其功能作用和调控机制未知。体外和体内实验研究发现，AOC4P能促进胃癌细胞增殖侵袭，并与其转录位点附近STAT3表达呈正相关，提示AOC4P可能顺式调节STAT3发挥作用。结合初步实验结果、生信预测分析和权威文献报道，我们推测C/EBPβ/AOC4P/LIN28B/IL-6正反馈环路通过调控STAT3促进胃癌增殖侵袭是潜在机制。本项目将在已有基础上，借助ChIP、RNA pulldown和RIP等多种实验技术，从临床样本、细胞和动物多个水平明确C/EBPβ/AOC4P/LIN28B/IL-6正反馈环路在胃癌中的功能作用，揭示分子间相互作用机制。项目的开展将丰富胃癌表观调控理论认知，有望取得具有转化前景的研究成果。

Long non-coding RNA plays a significant role in the progression of gastric cancer. lncRNA AOC4P, a relatively specific lncRNA in gastric cancer, has been shown the translational value for gastric cancer detection in our previous study, but its functional role and molecular mechanism still remains unknown. In vivo and in vitro experiment has found that lncRNA AOC4P could promote gastric cancer proliferation and invasion. The expression of lncRNA AOC4P was positively correlated with the expression of STAT3, which is the nearby gene of lncRNA AOC4P transcriptional loci, suggesting lncRNA AOC4P may function in cis via regulating STAT3. Based on bioinformatic analysis, previous solid evidence and experimental findings, we speculate C/EBPβ/AOC4P/LIN28B/IL-6 positive feedback circuit promote gastric cancer proliferation and invasion via STAT3. Based on our previous findings, by means of ChIP assay, RNA pulldown assay, RIP assays and other molecular techniques, the present project will investigate the role of C/EBPβ/AOC4P/LIN28B/IL-6 positive feedback circuit in gastric cancer, and elucidate the potential molecular interactions. The present project will enrich our knowledge about the epigenetic basis for gastric cancer and has a high possibility for clinical translation.