溃疡性结肠炎肠粘膜上皮细胞在慢性炎症持续的刺激下自噬功能表现异常,我们发现miR-29a调节ATG9A表达介导的细胞自噬起关键作用，导致肠粘膜修复及屏障功能严重受损。CircRNA大部分是充当miRNA的“吸附海绵”参与疾病的发生与发展。目前UC上皮细胞中circRNA差异表达谱不明，其如何调节miR-29a的表达而影响自噬相关基因ATG9A等表达机制未明。本项目拟分别从UC体外细胞学、DSS裸鼠模型、UC临床样本等三个研究层面，综合运用生物信息学系统、qRT-PCR、Western、FISH、染色质免疫沉淀、RNA结合蛋白免疫沉淀、circRNA pull-down、双荧光素酶报告基因、多色免疫荧光、免疫组化学等多种研究技术，验证circRNAs差异表达， circRNA竞争性结合miR-29a，并调控下游与自噬等有关的靶基因，促进UC上皮细胞凋亡导致患者预后不良的科学假设与与分子机制。

Ulcerative colitis intestinal mucosal epithelial cells exhibit abnormal autophagy function under the stimulation of chronic inflammation. We found that, the regulation of ATH9A by miR-29a plays an key role in autophagy, which results in serious damage to intestinal mucosal repair and barrier function. Most of CircRNA is involved in the occurrence and development of diseases as "adsorption sponges" of miRNAs. At present, the differential expression profile of circRNA in UC epithelial cells is unknown. How to regulate the expression of miR-29a and affect the expression mechanism of autophagy-related gene ATG9A is unknown. We plan to do the research in three levels: UC in vitro cytology, DSS nude mouse model, and collect UC clinical samples. And we intend to use bioinformatics systems, qRT-PCR, Western, FISH, chromatin immunoprecipitation, RNA-binding protein immunoprecipitation, CircRNA pull-down, dual luciferase reporter gene, multicolor immunofluorescence, immunohistochemistry and other research techniques to verify differential expression of circRNAs, circRNA competitively binds to miR-29a, and regulates downstream of autophagy-related target genes. The scientific hypothesis and molecular mechanism may affect the prognosis of UC patients.