Gastric cancer is one of the leading causes of cancer-related death worldwide. The transcription factor YY1 regulates diverse biological processes, including cell proliferation, development, DNA damage responses, and carcinogenesis. This study was designed to explore the role of YY1 regulated transcription in gastric cancer. YY1 silencing in gastric cancer cells has resulted in the inhibition of Wnt/β-catenin, JNK/MAPK, ERK/MAPK, ER, and HIF-1α signaling pathways. Genome-wide mRNA profiling upon silencing the expression YY1 gene in gastric cancer cells and comparison with the previously identified YY1 regulated genes from other lineages revealed a moderate overlap among the YY1 regulated genes. Despite the differing genes, all the YY1 regulated gene sets were expressed in most of the intestinal subtype gastric tumors and a subset of diffuse subtype gastric tumors. Integrative functional genomic analysis of the YY1 gene sets revealed an association among the pathways Wnt/β-catenin, Rapamycin, Cyclin-D1, Myc, E2F, PDGF, and AKT. Further, the drugs capable of inhibiting YY1 mediated transcription were identified as suitable targeted therapeutic candidates for gastric tumors with activated YY1. The data emerging from the investigation would pave the way for the development of YY1-based targeted therapeutics for gastric cancer.

胃癌是全世界与癌症相关的死亡的主要原因之一。转录因子YY1调节多种生物过程，包括细胞增殖，发育，DNA损伤反应和致癌作用。本研究旨在探讨YY1调控的转录在胃癌中的作用。胃癌细胞中的YY1沉默导致Wnt / β的抑制-catenin，JNK / MAPK，ERK / MAPK，ER和HIF-1α信号通路。沉默胃癌细胞中的YY1基因表达并与先前鉴定的来自其他谱系的YY1调控基因进行比较后，全基因组mRNA谱分析显示YY1调控基因之间存在中等重叠。尽管基因不同，但所有的YY1调控基因集都在大多数肠亚型胃肿瘤和一部分弥散性亚型胃肿瘤中表达。YY1基因组的综合功能基因组分析揭示了Wnt /β-catenin，雷帕霉素，Cyclin-D1，Myc，E2F，PDGF和AKT途径之间的关联。此外，鉴定出能够抑制YY1介导的转录的药物是具有激活的YY1的胃肿瘤的合适的靶向治疗候选物。