Harnessing the Power of Posttranscriptional Gene Silencing in Crohn's Disease.

Abstract

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, 4, 5, 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