Department of Gastroenterology, General Hospital of Nikea and Piraeus "Agios Panteleimon", Nikea, Greece.
Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Dig Liver Dis. 2017 Oct;49(10):1067-1072. doi: 10.1016/j.dld.2017.08.003. Epub 2017 Aug 9.
Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn's disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.
炎症性肠病(IBD)是一种多因素自身免疫性疾病,其患病率不断上升,但遗传、环境和免疫因素在其发病机制中的相互作用十分复杂,目前仍不明确。因此,我们非常有必要了解其发病机制,并开发出诊断和治疗工具。长链非编码 RNA(lncRNA)是长度大于 200 个核苷酸的 RNA 分子,已知其可干扰基因调控,但它们的作用和功能尚未完全阐明。尽管它们在癌症中的研究广泛,但对它们在其他疾病中的贡献知之甚少。越来越多的证据表明,lncRNA 在免疫系统的调控中起着关键作用,并且它们可干扰自身免疫性疾病(如 IBD)的发病机制。最近的研究已经确定了 IBD 相关基因附近的 lncRNA 以及 IBD 相关 lncRNA 中的单核苷酸多态性。此外,还分析了血液样本和活检组织,发现大量 lncRNA 在克罗恩病(CD)、溃疡性结肠炎(UC)或两者中均出现失调。(特别是在 UC 样本中,发现 INFG-AS1 和 BC012900 这两种 lncRNA 显著上调。同样,ANRIL 是一种包含不同疾病相关 SNP 的 lncRNA,在炎症性 IBD 组织中显著下调。)本文首次记录了在 IBD 中发现的失调 lncRNA 的最新数据,并讨论了提示性的发病机制,以及将 lncRNA 作为生物标志物的未来用途。