Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon.
Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon.
复制标题
直肠microRNA在结肠的小儿炎症性肠病中受到干扰。
DOI：
10.1016/j.crohns.2014.02.012
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发表时间：
2014-09
影响因子：
8
通讯作者：
Friedman, Joshua R.
中科院分区：
文献类型：
--
作者：
Zahm, Adam M.;Hand, Nicholas J.;Tsoucas, Daphne M.;Le Guen, Claire L.;Baldassano, Robert N.;Friedman, Joshua R.
关键词：
在患有溃疡性结肠炎或克罗恩病的成人患者中已经报道了肠道microRNA的变化。本研究的目的是确定与炎症性肠病儿童结肠炎相关的microRNA表达变化。直肠粘膜活检（n=50）和血液样本（n=47）收集已知或疑似炎症性肠病患者进行内窥镜检查。分别使用人nCounter®平台和TaqMan®低密度阵列平台对直肠和血清microRNA水平进行分析。然后通过定量RT-PCR在独立的样品组中验证显著改变的microRNA。在人结肠直肠Caco-2细胞系中进行体外荧光素酶报告基因测定，以确定miR-192对NOD 2表达的影响。直肠RNA的分析鉴定出21种microRNA在对照、UC和结肠CD样品组之间显著改变。选择用于验证的10种microRNA中有9种被确认为显著变化。与CD样本相比，UC中直肠miR-24增加了1.47倍（p=0.0052），并且是IBD亚型之间唯一改变的microRNA。三种结肠炎相关的microRNA在疾病患者的血清中显著改变，并显示出诊断效用。然而，没有发现血清microRNA来区分溃疡性结肠炎和克罗恩氏结肠炎。最后，miR-192抑制不影响荧光素酶报告基因活性，表明miR-192不调节人NOD 2。这项研究表明，直肠和血清microRNAs在小儿炎症性肠病中受到干扰。未来的研究确定炎症性肠病相关microRNAs的靶点可能会导致新的治疗方法。
Changes in intestinal microRNAs have been reported in adult patients with ulcerative colitis or Crohn’s disease. The goal of this study was to identify changes in microRNA expression associated with colitis in children with inflammatory bowel disease. Rectal mucosal biopsies (n=50) and blood samples (n=47) were collected from patients with known or suspected inflammatory bowel disease undergoing endoscopy. Rectal and serum microRNA levels were profiled using the human nCounter® platform and the TaqMan® low-density array platform, respectively. Significantly altered microRNAs were then validated in independent sample sets via quantitative RT-PCR. In vitro luciferase reporter assays were performed in the human colorectal Caco-2 cell line to determine the effect of miR-192 on NOD2 expression. Profiling of rectal RNA identified 21 microRNAs significantly altered between control, UC, and colonic CD sample groups. Nine of the ten microRNAs selected for validation were confirmed as significantly changed. Rectal miR-24 was increased 1.47-fold in UC compared to CD samples (p=0.0052) and was the only microRNA altered between IBD subtypes. Three colitis-associated microRNAs were significantly altered in the sera of disease patients and displayed diagnostic utility. However, no serum microRNAs were found to distinguish ulcerative colitis from Crohn’s colitis. Finally, miR-192 inhibition did not affect luciferase reporter activity, suggesting miR-192 does not regulate human NOD2. This study has demonstrated that rectal and serum microRNAs are perturbed in pediatric inflammatory bowel disease. Future studies identifying the targets of inflammatory bowel disease-associated microRNAs may lead to novel therapies.
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影响因子：
64.8
作者：
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.
通讯作者：
Bartel, David P.
影响因子：
29.4
作者：
McKenna LB;Schug J;Vourekas A;McKenna JB;Bramswig NC;Friedman JR;Kaestner KH
通讯作者：
Kaestner KH
影响因子：
3.7
作者：
Feng X;Wang H;Ye S;Guan J;Tan W;Cheng S;Wei G;Wu W;Wu F;Zhou Y
通讯作者：
Zhou Y
影响因子：
4.9
作者：
Heikenen, JB;Werlin, SL;Balint, JP
通讯作者：
Balint, JP
影响因子：
14.9
作者：
Griffiths-Jones, S
通讯作者：
Griffiths-Jones, S