溃疡性结肠炎中lncRNAs 的筛选、鉴定及其与miRNAs关系研究

We and others have found that short non-coding RNAs (microRNAs) play pivotal roles in pathogenesis of UC. Recent studies suggested that long non-coding RNA (lncRNAs) is associated with numerous human diseases. However, the role of lncRNAs in pathogenesis of IBD has not been disclosed. Our preliminary study for the first time observed differential expression of lncRNAs in active ulcerative colitis (UC), implicating lncRNAs as an important player for pathogenesis of UC. In this proposal, we aim to further understand the molecular mechanisms leading differential expression of lncRNAs in UC and the regulatory interplays between lncRNAs and miRNAs in pathogenesis of UC. We will first identify UC-associated lncRNAs and examine their potential roles as biomarkers for diagnosis and disease activity of UC patients. Further we will investigate the effects of cytokines and TLR agonists on expression of UC-associated lncRNAs, and determine their effects on core promoter elements of a lncRNA CDKN2B-AS. Finally, we will determine the regulatory mechanisms between CDKN2B-AS and miRNAs. Elucidation of the mechanisms of lncRNAs in UC pathogenesis will provide a fundamental basis for development of novel diagnostic and therapeutic approaches for UC and thus have a significant impact on clinical management of UC patients.

我们研究发现，短链非编码RNA(miRNAs)在溃疡性结肠炎(UC)的发病机制中起重要作用，而最近也有报道，长链非编码RNA(lncRNAs)与炎症性肠病(IBD)的发生发展亦有关，但其机制尚未明了。我们前期研究发现，活动期UC组织中存在lncRNAs差异表达，提示lncRNAs可能在UC的发病机制中发挥作用。本课题主要了解lncRNAs在UC中的差异表达及其分子调控机制，以及lncRNAs 与miRNAs 在UC中的相互作用机制。我们首先筛选、鉴定与UC相关的lncRNAs，并评价这些lncRNAs对UC诊断和其活动期判断的临床价值；其次，研究致炎因子、生长因子等对UC 相关lncRNA表达的影响，了解其对UC相关lncRNA CDKN2B-AS核心启动子序列的影响；最后探讨UC相关lncRNAs与miRNAs的相互作用及可能机制。这将为寻找UC新的诊断和治疗手段提供理论依据和实验基础。