Up-Regulation of microRNA-126 May Contribute to Pathogenesis of Ulcerative Colitis via Regulating NF-kappaB Inhibitor IκBα

Abstract

BackgroundMicroRNAs (miRNAs) are important post-transcriptional regulators. Altered expression of miRNAs has recently demonstrated association with human ulcerative colitis (UC). In this study, we attempted to elucidate the roles of miR-126 in the pathogenesis of UC.MethodsExpression of miR-126, miR-21, miR-375 and the potential targets NF-κB inhibitor alpha (IκBα, IKBA or NFKBIA), Polo-like kinase 2 (PLK2) and v-Crk sarcoma virus CT10 oncogene homolog (CRK) were assessed in 52 colonic biopsies from patients with active UC, inactive UC, irritable bowel syndrome (IBS) and from healthy subjects by quantitative RT-PCR and immunofluorescence analyses. Regulation of gene expression by miR-126 was assessed using luciferase reporter construct assays and specific miRNA mimic transfection.ResultsWe found that the expression of miR-126 and miR-21 were significantly increased in active UC group compared to the inactive UC, IBS and healthy control groups (P<0.05). In contrast, the expression of IKBA mRNA and protein was remarkably decreased in the active UC group compared with the other three groups (P<0.05). The expression of miR-126 and IKBA mRNA were inversely correlated in active UC patients (P<0.05). However the expression of miR-375, PLK2 and CRK showed no difference between each group. Furthermore, we demonstrate that endogenous miR-126 and exogenous miR-126 mimic can inhibit IκBα expression. Finally, mutating the miR-126 binding site of the IKBA 3′-UTR reporter construct restored reporter gene expression.ConclusionmiR-126 may play roles in UC inflammatory activity by down-regulating the expression of IKBA, an important inhibitor of NF-κB signaling pathway.

miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

“…Furthermore, they found that miR192 participated in the regulation of chemokine production in colonic epithelial cells. Since 2008, some new research in active UC and healthy controls has confirmed the upregulation of miR-21 [25,118] , miR 29a [119] , and miR126 [120] , and identified additional upregulated miRNAs, including miR7, miR29b, miR126*, miR1273p, miR135b, miR223 and miR 3243p [119] , miR31 [119,121] , miR150 [26] , miR155 [118] , miR146a, miR206, and miR424 [121] , and miR 20b and miR125b1* [122] . In contrast, miR1885p, miR215, miR320a, miR346 [119] , and miR200b [123] were downregulated in colon tissues from active UC patients compared with healthy controls.…”

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review

“…Feng et al [24] proved that up-regulation of miR-126 may contribute to pathogenesis of UC by targeting IκBα. They found miR-126 was significantly increased in active UC tissues compared to healthy controls.…”

Investigation of significant microRNA-mRNA pairs associated with nonspecific digestive disorder in rabbits

“…In this study, 6 genes (IκBα, NLRP3, NLRP12, NUMB, SIAH2, TLR4) and 4 miRNAs (miR-122, miR-192, miR-146a, miR-126) related to innate immune system were significantly differentially expressed among groups. Over-expression of miR-126 leads to NF-κB activation via down-regulation of IκBα, which may contribute to the pathogenesis of human UC (Feng et al, 2012). The miR-146a targeted NUMB gene and alleviated the suppression of SHH signalling to amplify inflammatory responses of IBD (Ghorpade et al, 2013;Nata et al, 2013).…”

“…IBD or NSDD-related 25 genes and 25 miRNAs were retrieved from published papers Feng et al, 2012;Ghorpade et al, 2013;Koukos et al, 2013;Liu et al, 2013;Nata et al, 2013;Yang et al, 2013aYang et al, , 2013b Zhang et al, 2013;Fu et al, 2014;Lu et al, 2014;Carethers et al, 2015;Fu et al, 2015;Kalla et al, 2015), and their expression levels were then detected by RT-qPCR method in ileum, RSR and colon tissues. The relative expression level of the genes and miRNAs are shown in Figure 1 and Figure 2, in which the highest expression one is set to 1.…”