Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα.
Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα.
复制标题
DOI：
10.1371/journal.pone.0052782
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Feng X;Wang H;Ye S;Guan J;Tan W;Cheng S;Wei G;Wu W;Wu F;Zhou Y
MicroRNA (miRNA) 是重要的转录后调节因子。最近证明 miRNA 表达的改变与人类溃疡性结肠炎 (UC) 相关。在本研究中，我们试图阐明 miR-126 在 UC 发病机制中的作用。在 52 例活动性 UC、非活动性 UC、肠易激综合征 (IBS) 和通过定量 RT-PCR 和免疫荧光分析从健康受试者中提取。使用荧光素酶报告基因构建分析和特定 miRNA 模拟转染评估 miR-126 对基因表达的调节。我们发现，与非活动性UC、IBS和健康对照组相比，活动性UC组中miR-126和miR-21的表达显着升高（P<0.05）。相比之下，活动性UC组IKBA mRNA和蛋白表达量较其他三组显着降低（P<0.05）。活动性UC患者中miR-126和IKBA mRNA的表达呈负相关（P<0.05）。然而，各组之间miR-375、PLK2和CRK的表达没有差异。此外，我们证明内源性 miR-126 和外源性 miR-126 模拟物可以抑制 IκBα 表达。最后，突变 IKBA 3'-UTR 报告构建体的 miR-126 结合位点恢复了报告基因表达。 miR-126可能通过下调NF-κB信号通路重要抑制剂IKBA的表达在UC炎症活动中发挥作用。
MicroRNAs (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. Expression 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. We 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. miR-126 may play roles in UC inflammatory activity by down-regulating the expression of IKBA, an important inhibitor of NF-κB signaling pathway.
登录
查看更多内容
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
3.1
作者：
Szamosi, Tamas;Lakatos, Peter Laszlo;Andrikovics, Hajnalka
通讯作者：
Andrikovics, Hajnalka
DOI：
10.1073/pnas.0905063106
发表时间：
2009-11-03
影响因子：
11.1
作者：
Mattes, Joerg;Collison, Adam;Foster, Paul S.
通讯作者：
Foster, Paul S.
影响因子：
3.5
作者：
Lawrance, IC;Fiocchi, C;Chakravarti, S
通讯作者：
Chakravarti, S
DOI：
10.1073/pnas.0808266105
发表时间：
2008-10-07
影响因子：
11.1
作者：
Li, Zejuan;Lu, Jun;Chen, Jianjun
通讯作者：
Chen, Jianjun