Research Laboratories, Bambino Gesù Children's Hospital-IRCCS, V.le di San Paolo 15, 00146 Rome, Italy.
Int J Mol Sci. 2017 Sep 6;18(9):1907. doi: 10.3390/ijms18091907.
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression at the post-transcriptional level and play a key role in the pathogenesis of autoimmune and gastrointestinal diseases. Previous studies have revealed that miRNAs are dysregulated in intestinal biopsies of patients affected by coeliac disease (CD). Combined bioinformatics analyses of miRNA expression profiles and mRNA target genes as classified by Gene Ontology, are powerful tools to investigate the functional role of miRNAs in coeliac disease. However, little is still known about the function of circulating miRNAs, their expression level compared to tissue miRNAs, and whether the mechanisms of post-transcriptional regulation are the same of tissue miRNAs. In any case, if we assume that a cell-cell communication process has to occur, and that circulating miRNAs are delivered to recipient cells, we can derive useful information by performing target predictions. Interestingly, all of the mRNA targets of dysregulated miRNAs reported in the literature (i.e., miR-31-5p, miR-192, miR-194, miR-449a and miR-638) belong to several important biological processes, such as Wnt signaling, cell proliferation and differentiation, and adherens junction pathways. Although we think that these predictions have to be necessarily confirmed by "wet-lab" data, the miRNAs dysregulated during the development of CD could be potentially involved in the pathogenesis of coeliac disease and their correlation with circulating miRNAs offers new possibilities to use them as disease biomarkers.
微小 RNA(miRNAs)是短的非编码 RNA,在转录后水平调节基因表达,在自身免疫和胃肠道疾病的发病机制中发挥关键作用。先前的研究表明,在患有乳糜泻(CD)的患者的肠道活检中,miRNAs 存在失调。miRNA 表达谱和基因本体论分类的 mRNA 靶基因的联合生物信息学分析是研究 miRNA 在乳糜泻中的功能作用的有力工具。然而,对于循环 miRNA 的功能、其与组织 miRNA 的表达水平以及是否具有相同的转录后调控机制,我们仍然知之甚少。在任何情况下,如果我们假设必须发生细胞间通讯过程,并且循环 miRNA 被递送到受体细胞,那么通过进行靶基因预测,我们可以获得有用的信息。有趣的是,文献中报道的失调 miRNA 的所有 mRNA 靶基因(即 miR-31-5p、miR-192、miR-194、miR-449a 和 miR-638)都属于几个重要的生物学过程,如 Wnt 信号、细胞增殖和分化以及黏着连接途径。尽管我们认为这些预测必须通过“湿实验室”数据来证实,但在 CD 发展过程中失调的 miRNAs 可能潜在地参与乳糜泻的发病机制,并且它们与循环 miRNAs 的相关性为将其用作疾病生物标志物提供了新的可能性。