Integrated microRNA and messenger RNA analysis in aortic stenosis.
Integrated microRNA and messenger RNA analysis in aortic stenosis.
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DOI：
10.1038/srep36904
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发表时间：
2016-11-23
影响因子：
4.6
通讯作者：
Jones GT
中科院分区：
文献类型：
--
作者：
Coffey S;Williams MJ;Phillips LV;Galvin IF;Bunton RW;Jones GT
主动脉瓣狭窄(AS)是发病率和死亡率的主要原因，目前尚无有效的药物治疗方法。由于难以获得健康的瓣膜组织作为对照组，对人类AS潜在生物学的研究受到限制。然而，微核糖核酸(MiRNAs)在死后组织中是稳定的。我们比较了行主动脉瓣膜置换术的患者的瓣膜标本和未患病的身体瓣膜。我们在微阵列分析中发现了106个差异表达的miRNA(p <； 0.05，经多次比较调整后)，在上调和下调的miRNA中表达高度相关。结合miRNA/基因表达分析验证了芯片结果的整体，定量聚合酶链式反应证实miR-122-5p、miR-625-5p、miR-30e-5p下调，miR-21-5p和miR-221-3p上调。对整合的miRNA/mRNA网络的通路分析确定了主要参与细胞外基质功能的通路。目前一些可用的治疗方法针对整合的miRNA/mRNA网络中上调基因的产物，这些基因主要是网络中更外围的成员。识别一组与AS相关的组织miRNA可能有助于开发新的AS治疗方法。这项研究强调了以系统生物学为基础的方法对复杂疾病的重要性。
Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no effective medical therapies. Investigation into the underlying biology of AS in humans is limited by difficulties in obtaining healthy valvular tissue for use as a control group. However, micro-ribonucleic acids (miRNAs) are stable in post-mortem tissue. We compared valve specimens from patients undergoing aortic valve replacement for AS to non-diseased cadaveric valves. We found 106 differentially expressed miRNAs (p < 0.05, adjusted for multiple comparisons) on microarray analysis, with highly correlated expression among up- and down-regulated miRNAs. Integrated miRNA/gene expression analysis validated the microarray results as a whole, while quantitative polymerase chain reaction confirmed downregulation of miR-122-5p, miR-625-5p, miR-30e-5p and upregulation of miR-21-5p and miR-221-3p. Pathway analysis of the integrated miRNA/mRNA network identified pathways predominantly involved in extracellular matrix function. A number of currently available therapies target products of upregulated genes in the integrated miRNA/mRNA network, with these genes being predominantly more peripheral members of the network. The identification of a group of tissue miRNA associated with AS may contribute to the development of new therapeutic approaches to AS. This study highlights the importance of systems biology-based approaches to complex diseases.
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影响因子：
25.7
作者：
Li, Jiang;Ghazwani, Mohammed;Zhang, Yifei;Lu, Jianqin;Li, Jilong;Fan, Jie;Gandhi, Chandrashekhar R.;Li, Song
通讯作者：
Li, Song
影响因子：
5.7
作者：
Coffey, Sean;Cairns, Benjamin J.;Iung, Bernard
通讯作者：
Iung, Bernard
影响因子：
4.6
作者：
Jian, B;Narula, N;Levy, RJ
通讯作者：
Levy, RJ
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
158.5
作者：
Cowell, SJ;Newby, DE;Boon, NA
通讯作者：
Boon, NA