miR-939和miR-376a作为转录因子圈套对溃疡性结肠炎基因表达调控的作用及机制研究

微小核糖核酸（miRNAs）已被证实对基因表达具有转录后抑制作用，但目前尚无miRNA对基因表达转录过程中调控的报道。申请人在前期实验研究中发现了miRNAs的一个新的非经典转录调节机制----miR-939和miR-376a可以作为一种转录因子（TFs）内源性“圈套”，实现在转录水平上靶向性调控基因表达，能针对溃疡性结肠炎（UC）的多种机制进行抑制或阻断。本课题拟在前期实验基础上，从基础回归到临床中验证miR-939和miR-376A在UC病人体液中的表达情况；利用miR-939和miR-376A对于NF-κB和NFAT的圈套策略，分析其对炎性因子的表达影响；进一步解析圈套策略对于UC时肠屏障的紧密连接和通透性的恢复作用；探讨圈套策略对于靶细胞凋亡的抑制作用；观察圈套策略对于UC模型小鼠的治疗作用。本项目的开展不仅可以补充UC发病的机制理论基础，更将为日后临床开展对UC的治疗提供新思路。

The inhibition effect of MicroRNAs on gene expression at a posttranscriptional level have been verified.However, there are still no reports indicate that micrornas can regulate gene expression in the process of transcription regulation. In our previous research,we found a new non-classical transcriptional regulation mechanism of miRNAs,that miR-939 and miR–376a as kinds of transcription factors (TFs) endogenous "trap",can targeting regulate gene expression in the process of transcription regulation and block or suppress a variety of mechanisms of ulcerative colitis (UC). We will turn to clinic to assess the expression of miR-939 and miR–376a on the basis of preliminary experiments.Analyze the influence of miR-939 and miR-376a on -inflammatory factor expression by miR-939 and miR-376a’s trap strategy on the nf-kappa B and the NFAT. Furthermore, try to analyze the trap strategy’s inhibitory effect on intestinal harrier(tight junction and the permeability of intestinal walls),analyze the trap strategy’s inhibitory effect on target cell apoptosis.The effect on uc mices will be observed.Our project isn’t just a complement of pathogenesis of UC mechanism, but also a possibility for the future clinical treatment of UC.