新近研究显示：启动子相关非编码RNA(pancRNA)能以RNA-蛋白质相互作用方式，影响转录调节蛋白的活性，调控基因表达。我们前期发现：E26转化特异性因子1(Ets-1)能促进胃癌侵袭转移及血管生成；Ets-1启动子区域存在的非编码RNA(pancEts-1)能结合转录因子CCCTC结合因子(CTCF)，阻遏CTCF对胃癌中Ets-1表达的抑制作用，但其内在机制不明。本项目拟进一步观测CTCF招募组蛋白去乙酰化酶导致的染色质重塑对胃癌Ets-1表达的调控作用，解析pancEts-1与CTCF相互作用的结构域，明确pancEts-1对CTCF结合至Ets-1启动子、Ets-1基因转录的影响，观测pancEts-1稳定过表达/抑制、Ets-1表达回补体系对胃癌细胞体内外侵袭转移及血管生成的影响，旨在从新型内源性pancRNA角度阐明Ets-1表达调控机理，为胃癌的治疗提供新途径和理论基础。

Recent evidence shows that promoter-associated non-coding RNAs (pancRNAs) are able to impact the activity of transcription regulatory proteins through RNA-protein interaction, and subsequently regulate gene expression. Our previous studies have indicated that E26 transformation-specific-1 (Ets-1) facilitates the invasion, metastasis, and angiogenesis of gastric cancer. The Ets-1 promoter-associated non-coding RNA (pancEts-1) might bind transcription factor CCCTC-binding factor (CTCF) and inhibit the CTCF-mediated repression on Ets-1 expression in gastric cancer. However, the underlying mechanisms still remain to be determined. This project is proposed to further observe the regulatory effects of CTCF-mediated recruitment of histone deacetylases and chromosome remodeling on Ets-1 expression, and elucidate the interaction domains between pancEts-1 and CTCF in gastric cancer. The impacts of pancEts-1 on the binding of CTCF on Ets-1 promoter and Ets-1 gene transcription will also be explored in gastric cancer. In addition, the in vitro and in vivo invasion, metastasis, and angiogenesis of gastric cancer cells will be studied through stable over-expression or knockdown of pancEts-1 and Ets-1 rescue experiments. This study will elucidate the crucial roles of endogenous pancRNA in regulating the Ets-1 expression, and will provide a novel approach and theoretical basis for the therapeutics of gastric cancer.