MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis.
MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis.
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MicroRNA-124调节STAT3表达，并在小儿溃疡性结肠炎患者的结肠组织中下调。
DOI：
10.1053/j.gastro.2013.07.001
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发表时间：
2013-10
期刊：
影响因子：
29.4
通讯作者：
Iliopoulos D
中科院分区：
文献类型：
--
作者：
Koukos G;Polytarchou C;Kaplan JL;Morley-Fletcher A;Gras-Miralles B;Kokkotou E;Baril-Dore M;Pothoulakis C;Winter HS;Iliopoulos D
microRNA（miRs）水平和功能的改变与炎症性肠病（IBD）相关，尽管对其在儿科IBD中的作用知之甚少。我们研究了溃疡性结肠炎（UC）儿童的结肠粘膜miR是否发生改变。我们使用316个miR库来鉴定那些调节与白细胞介素-6孵育的NCM 460人结肠细胞中STAT 3磷酸化的miR。通过实时PCR分析来自患有UC的儿童和成人患者以及没有IBD的患者（对照）的结肠活检组织以及与5-氮杂-2 '-脱氧胞苷孵育的HCT-116结肠细胞来测量miR-124的水平。通过定量甲基化特异性PCR测量MIR 124启动子的甲基化。与对照组织相比，UC儿科患者中磷酸化STAT 3及其调节的基因（编码VEGF、BCL 2、BCL XL和MMP 9）水平升高。miR-124、let-7、miR-125、miR-26或miR-101的过表达使NCM 460细胞中的STAT 3磷酸化降低≥75%; miR-124的作用最大。miR-124在儿童UC患者的结肠组织中特异性下调，并直接靶向STAT 3 mRNA。与非活动期UC患者相比，活动期UC儿童患者结肠组织中miR-124水平降低，而STAT 3磷酸化水平升高。此外，在实验性结肠炎小鼠中，miR-124和STAT 3的水平呈负相关。UC儿童组织中miR-124的下调归因于其启动子区域的高甲基化。用5-氮杂-2 '脱氧胞苷孵育HCT-116结肠细胞上调miR-124并降低STAT 3 mRNA水平。miR-124似乎调节STAT 3的表达。活动期UC患儿结肠组织中miR-124水平的降低似乎增加了STAT 3的表达和活性，这可能促进儿童UC的炎症和发病。
Altered levels and functions of microRNAs (miRs) have been associated with inflammatory bowel diseases (IBDs), although little is known about their roles in pediatric IBD. We investigated whether colonic mucosal miRs are altered in children with ulcerative colitis (UC). We used a library of 316 miRs to identify those that regulate phosphorylation of STAT3 in NCM460 human colonocytes incubated with interleukin-6. Levels of miR-124 were measured by real-time PCR analysis of colon biopsies from pediatric and adult patients with UC and patients without IBD (controls), and of HCT-116 colonocytes incubated with 5-aza-2’-deoxycytidine. Methylation of the MIR124 promoter was measured by quantitative methylation-specific PCR. Levels of phosphorylated STAT3 and the genes it regulates (encoding VEGF, BCL2, BCLXL, and MMP9) were increased in pediatric patients with UC, compared to control tissues. Overexpression of miR-124, let-7, miR-125, miR-26, or miR-101 reduced STAT3 phosphorylation by ≥75% in NCM460 cells; miR-124 had the greatest effect. miR-124 was downregulated specifically in colon tissues from pediatric patients with UC and directly targeted STAT3 mRNA. Levels of miR-124 were decreased whereas levels of STAT3 phosphorylation increased in colon tissues from pediatric patients with active UC, compared to those with inactive disease. Furthermore, levels of miR-124 and STAT3 were inversely correlated in mice with experimental colitis. Downregulation of miR-124 in tissues from children with UC was attributed to hypermethylation of its promoter region. Incubation of HCT-116 colonocytes with 5-aza-2’ deoxycytidine upregulated miR-124 and reduced levels of STAT3 mRNA. MiR-124 appears to regulate the expression of STAT3. Reduced levels of miR-124 in colon tissues of children with active UC appear to increase expression and activity of STAT3, which could promote inflammation and pathogenesis of UC in children.
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影响因子：
64.5
作者：
Hatziapostolou M;Polytarchou C;Aggelidou E;Drakaki A;Poultsides GA;Jaeger SA;Ogata H;Karin M;Struhl K;Hadzopoulou-Cladaras M;Iliopoulos D
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