Harnessing the Power of Posttranscriptional Gene Silencing in Crohn's Disease.
Harnessing the Power of Posttranscriptional Gene Silencing in Crohn's Disease.
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利用转录后基因沉默的力量治疗克罗恩病。
DOI：
10.1038/ctg.2016.5
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发表时间：
2016
影响因子：
3.6
通讯作者：
Sheikh,ShehzadZ
中科院分区：
文献类型：
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作者：
Abdalla,Maisa;Sheikh,ShehzadZ
转录后基因沉默或RNA干扰是一种非编码RNA，特别是小RNA部分或完全抑制一个或多个基因表达的机制。在实验室中，这一概念已被用于引入合成的反微RNA(MiRNA)寡核苷酸来下调或完全取消基因表达。MiRNAs是一组小的(~22个核苷酸)的非编码RNA，负责对基因表达的转录后调节。1它们已成为多种生物过程的关键调节剂，也是候选的治疗靶点。MiRNAs通过与靶向线粒体RNA的3‘非翻译区(UTR)内的靶点结合，使基因沉默。这会抑制蛋白质合成和/或转录本的降解。一些miRNAs已经被确定为克罗恩病(CD)发病机制的调节因子。2例如，已证明miR-192、miR-122、miR-29和miR-146a靶向并抑制CD中涉及的NOD2。3-6利用小RNA测序，在结肠组织中发现了一套miRNAs，它们根据疾病行为对CD患者进行分层，与炎症的影响无关。此外，这些患者中特定的miRNAs水平可以预测CD穿透和瘘管形成的进展。7这篇简短综述的目的是强调利用转录后基因沉默来理解和治疗CD的进展。8、9
Posttranscriptional gene silencing or RNA interference is a mechanism by which the expression of one or more genes is partially or fully suppressed by noncoding RNAs, particularly small RNAs. In the laboratory this concept has been utilized to introduce synthetic anti-microRNA (miRNA) oligonucleotides to downregulate or completely abrogate gene expression. MiRNAs are a group of small (~ 22 nucleotide), noncoding RNAs that confer such posttranscriptional regulation of gene expression. 1 They have emerged as key regulators of a wide variety of biological processes and also as candidate therapeutic targets. MiRNAs silence genes by binding to target sites found within the 3′ untranslated region (UTR) of the targeted mitochondrial RNA. This results in the suppression of protein synthesis and/or degradation of the transcript. A number of miRNAs have already been identified as regulators of pathways that underlie the pathogenesis of Crohn’s Disease (CD). 2 For example, miR-192, miR-122, miR-29, and miR-146a have been shown to target and repress NOD2, which has been implicated in CD. 3–6 Using small RNA-sequencing a suite of miRNAs were identified in colon tissue that stratify CD patients according to disease behavior independent of the effect of inflammation. Furthermore, levels of specific miRNAs in these patients could predict progression to penetrating and fistulizing CD. 7 The purpose of this short review is to highlight the advances in using posttranscriptional gene silencing in understanding and treating CD. 8, 9