3D基因组调节已成为未来肿瘤生物学新的研究方向。MeCP2/CTCF是重要的染色质重塑因子，参与染色质构象改变，调控基因表达。前期工作与生物信息学分析表明胃癌中RBBP8与MeCP、CTCF表达分别呈负相关和正相关；沉默MeCP2或CTCF分别上调或下调RBBP8表达；CTCF在RBBP8增强子/启动子区有结合位点，MeCP2在RBBP8启动子区有结合位点，它们启动子区结合位点重合，提出MeCP2/CTCF通过染色质重塑竞争性调控RBBP8表达影响胃癌进展。本研究拟收集胃癌样本分析MeCP2、CTCF和RBBP8表达的临床意义；应用RNAi、ChIP、3C、ChIA-PET、报告基因等研究MeCP2/CTCF对RBBP8启动子/增强子拓扑关联的竞争调控机制，RBBP8对细胞周期调控因子的调节；建立荷瘤裸鼠模型验证。研究结果将为3D基因组在胃癌中的调控机制提供新证据，并为胃癌治疗提供新靶点。

Three-dimensional (3D) genome regulation has become a new research direction of tumor biology in the future. MeCP2/CTCF are important chromatin remodeling factors, which are involved in conformational changes of chromatin and regulate gene expressions. Our previous research and bioinformatics analysis showed that RBBP8 was negatively and positively correlated with MeCP and CTCF expression in gastric cancer, respectively. Silencing MeCP2 up-regulated RBBP8 expression, while silencing CTCF down-regulated RBBP8 expression. Silencing MeCP2 and CTCF, or overexpressing MeCP2 and CTCF, both recovered the RBBP8 expression to normal level. Bioinformatics analysis and MeCP2-ChIP-seq result discovered that there are CTCF binding sites in the RBBP8 enhancer/promoter region, and MeCP2 binding site in the RBBP8 promoter region, and their binding sites coincide with each other in the promoter region. Bioinformatics data also showed that the methylation level of 3 CpG sites in the RBBP8 promoter region was negatively correlated with the expression of RBBP8. 5-azacytidine (5-aza), a methylation inhibitor, inhibited the expression of RBBP8. ChIP-RT-PCR experiment revealed that MeCP2 antibody captured the binding site of RBBP8 promoter region, and CTCF antibody captured the binding sites of promoter and enhancer region. Therefore, we proposed that MeCP2/CTCF could competitively regulate RBBP8 expression through chromatin remodification to affect gastric cancer progression. In the present study, the clinical significance of MeCP2, CTCF, and RBBP8 in gastric cancer is observed using immunohistochemical, immunoblotting, and quantitive real-time PCR analysis. Then RNAi, ChIP-seq, ChIP-PCR, 3C, ChIA-PET, and reporter assay are applied to explore the mechanism of MeCP2/CTCF competitivly regulating RBBP8 promoter/enhancer, and the regulation mechanism of cell cycle regulators by RBBP8. Next, roles of MeCP2, CTCF, and RBBP8 in the cell proliferation, cell cycle, apoptosis, invasion, and migration of gastric cancer cells are studied by MTT, colony forming experiment, and flow cytometry. Finally, the mechanism of MeCP2/CTCF competitivly regulating RBBP8 expression is explored in vivo using nude mice. We aim to explore the roles of MeCP2/CTCF-RBBP8-cycle regulator axis and the regulation mechanism in gastric cancer development and progression, which will provide a new evidence for the regulation mechanism of 3D genome in gastric cancer and provide new targets for the treatment of gastric cancer.