High-Throughput Sequencing of microRNAs in Glucocorticoid Sensitive Paediatric Inflammatory Bowel Disease Patients.
High-Throughput Sequencing of microRNAs in Glucocorticoid Sensitive Paediatric Inflammatory Bowel Disease Patients.
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DOI：
10.3390/ijms19051399
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发表时间：
2018-05-08
影响因子：
5.6
通讯作者：
Decorti G
中科院分区：
文献类型：
--
作者：
De Iudicibus S;Lucafò M;Vitulo N;Martelossi S;Zimbello R;De Pascale F;Forcato C;Naviglio S;Di Silvestre A;Gerdol M;Stocco G;Valle G;Ventura A;Bramuzzo M;Decorti G
本研究的目的是鉴定新的药物基因组学生物标志物，以更好地了解糖皮质激素（GC）在儿科炎症性肠病（IBD）中作用的复杂基因调控机制。这一目标是通过评估GC治疗期间的高通量microRNA（miRNA）谱，结合GC受体（GR）异源复合物基因表达变化的评估来实现的。此外，我们通过研究其基因启动子中GC响应元件（GRES）的存在，验证了差异表达的miRNA可以直接受GC调控的假设。入组了10例对GC有反应的IBD儿科患者。在诊断时（T0）和类固醇治疗四周后（T4）采集外周血。使用下一代测序分析microRNA谱，并通过定量逆转录-聚合酶链反应验证选择的显著差异表达的miRNA。T0 ~ T4共检测到18个差异表达的miRNAs，其中16个上调，2个下调。其中，三种miRNAs miR-144、miR-142和miR-96可识别GR基因的3 'UTR，（miR-363、miR-96、miR-142）含有GR序列，从而潜在地能够通过GR进行直接调节。我们鉴定了在GC治疗过程中不同表达的miRNAs，以及在年轻IBD患者的血细胞中可由GC直接调节的miRNAs。这些结果可能代表了将其翻译为药物基因组学生物标志物的第一步。
The aim of this research was the identification of novel pharmacogenomic biomarkers for better understanding the complex gene regulation mechanisms underpinning glucocorticoid (GC) action in paediatric inflammatory bowel disease (IBD). This goal was achieved by evaluating high-throughput microRNA (miRNA) profiles during GC treatment, integrated with the assessment of expression changes in GC receptor (GR) heterocomplex genes. Furthermore, we tested the hypothesis that differentially expressed miRNAs could be directly regulated by GCs through investigating the presence of GC responsive elements (GREs) in their gene promoters. Ten IBD paediatric patients responding to GCs were enrolled. Peripheral blood was obtained at diagnosis (T0) and after four weeks of steroid treatment (T4). MicroRNA profiles were analyzed using next generation sequencing, and selected significantly differentially expressed miRNAs were validated by quantitative reverse transcription-polymerase chain reaction. In detail, 18 miRNAs were differentially expressed from T0 to T4, 16 of which were upregulated and 2 of which were downregulated. Out of these, three miRNAs (miR-144, miR-142, and miR-96) could putatively recognize the 3’UTR of the GR gene and three miRNAs (miR-363, miR-96, miR-142) contained GREs sequences, thereby potentially enabling direct regulation by the GR. In conclusion, we identified miRNAs differently expressed during GC treatment and miRNAs which could be directly regulated by GCs in blood cells of young IBD patients. These results could represent a first step towards their translation as pharmacogenomic biomarkers.
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DOI：
10.1093/bioinformatics/btr064
发表时间：
2011-04-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Grant CE;Bailey TL;Noble WS
通讯作者：
Noble WS
影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
7.6
作者：
Raddatz, D;Middel, P;Ramadori, G
通讯作者：
Ramadori, G
影响因子：
3
作者：
Risso D;Schwartz K;Sherlock G;Dudoit S
通讯作者：
Dudoit S
影响因子：
14.9
作者：
Hsu SD;Tseng YT;Shrestha S;Lin YL;Khaleel A;Chou CH;Chu CF;Huang HY;Lin CM;Ho SY;Jian TY;Lin FM;Chang TH;Weng SL;Liao KW;Liao IE;Liu CC;Huang HD
通讯作者：
Huang HD