Asthma MicroRNA Regulome Development Using Validated miRNA-Target Interaction Visualization

被引:8
作者
Fekonja, Simon [1 ]
Korosec, Peter [2 ]
Rijavec, Matija [2 ]
Jesenicnik, Taja [3 ]
Kunej, Tanja [1 ]
机构
[1] Univ Ljubljana, Biotech Fac, Dept Anim Sci, Domzale 1230, Slovenia
[2] Univ Clin Resp & Allerg Dis Golnick, Lab Clin Immunol & Mol Genet, Golnik, Slovenia
[3] Univ Ljubljana, Biotech Fac, Agron Dept, Ljubljana, Slovenia
关键词
asthma; epigenomics; biomarkers; microRNA; regulome; AIRWAY SMOOTH-MUSCLE; BRONCHIAL EPITHELIAL-CELLS; CD4(+) T-CELLS; MEDIATED REGULATION; ALLERGIC DISEASES; PEDIATRIC ASTHMA; EXPRESSION; PROLIFERATION; INFLAMMATION; CYTOKINE;
D O I
10.1089/omi.2018.0112
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Asthma is a common multifactorial complex disease caused by an interaction of genetic and environmental factors. There are no robust biomarkers or molecular diagnostics for asthma or its detailed phenotypic stratification in the clinic. Regulatory and epigenomic factors are priority candidates for asthma biomarker discovery and translational research because this common disease emerges in association with host/environment interactions. In this context, epigenomic molecular events such as microRNA (miRNA) silencing affect asthma susceptibility and severity. We report here an analysis of the miRNAs in the literature, their targets associated with asthma, and present the findings organized as an miRNA-target network, an miRNA regulome of asthma. The miRNA-target interactions in asthma were extracted from the PubMed and the Web of Science databases, while the miRNA-target network was visualized with the Cytoscape tool. Genomic locations of miRNA and target genes were displayed using the Ensembl Whole Genome tool. We cataloged miRNAs associated with asthma and their experimentally validated targets, retrieving 48 miRNAs associated with asthma, and 54 experimentally validated miRNA targets. Four central molecules involved in 34.5% of all interactions were identified in the network. The miRNA-target pairs were constructed as an asthma-associated miRNA-target regulatory network. The network revealed subnetworks pointing toward potential asthma biomarker candidates. The asthma miRNA regulome reported here offers a strong foundation for future translational research and systems medicine applications for asthma diagnostic and therapeutic innovation. Developed protocol for constructing miRNA regulome could now be used for biomarker development in multifactorial diseases.
引用
收藏
页码:607 / 615
页数:9
相关论文
共 69 条
[31]   miR-125b inhibits goblet cell differentiation in allergic airway inflammation by targeting SPDEF [J].
Liu, Zhaoe ;
Chen, Xing ;
Wu, Qiaoling ;
Song, Jia ;
Wang, Lijun ;
Li, Gang .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2016, 782 :14-20
[32]   Function of miR-146a in Controlling Treg Cell-Mediated Regulation of Th1 Responses [J].
Lu, Li-Fan ;
Boldin, Mark P. ;
Chaudhry, Ashutosh ;
Lin, Ling-Li ;
Taganov, Konstantin D. ;
Hanada, Toshikatsu ;
Yoshimura, Akihiko ;
Baltimore, David ;
Rudensky, Alexander Y. .
CELL, 2010, 142 (06) :914-929
[33]   Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein [J].
Lu, Li-Fan ;
Thai, To-Ha ;
Calado, Dinis Pedro ;
Chaudhry, Ashutosh ;
Kubo, Masato ;
Tanaka, Kentaro ;
Loeb, Gabriel B. ;
Lee, Hana ;
Yoshimura, Akihiko ;
Rajewsky, Klaus ;
Rudensky, Alexander Y. .
IMMUNITY, 2009, 30 (01) :80-91
[34]   Diagnostic, functional, and therapeutic roles of microRNA in allergic diseases [J].
Lu, Thomas X. ;
Rothenberg, Marc E. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2013, 132 (01) :3-13
[35]   miR-223 Deficiency Increases Eosinophil Progenitor Proliferation [J].
Lu, Thomas X. ;
Lim, Eun-Jin ;
Besse, John A. ;
Itskovich, Svetlana ;
Plassard, Andrew J. ;
Fulkerson, Patricia C. ;
Aronow, Bruce J. ;
Rothenberg, Marc E. .
JOURNAL OF IMMUNOLOGY, 2013, 190 (04) :1576-1582
[36]   MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers [J].
Lu, Thomas X. ;
Sherrill, Joseph D. ;
Wen, Ting ;
Plassard, Andrew J. ;
Besse, John A. ;
Abonia, Juan Pablo ;
Franciosi, James P. ;
Putnam, Philip E. ;
Eby, Michael ;
Martin, Lisa J. ;
Aronow, Bruce J. ;
Rothenberg, Marc E. .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2012, 129 (04) :1064-U593
[37]   MicroRNA-21 Is Up-Regulated in Allergic Airway Inflammation and Regulates IL-12p35 Expression [J].
Lu, Thomas X. ;
Munitz, Ariel ;
Rothenberg, Marc E. .
JOURNAL OF IMMUNOLOGY, 2009, 182 (08) :4994-5002
[38]   Asthma inflammatory phenotypes show differential microRNA expression in sputum [J].
Maes, Tania ;
Cobos, Francisco Avila ;
Schleich, Florence ;
Sorbello, Valentina ;
Henket, Monique ;
De Preter, Katleen ;
Bracke, Ken R. ;
Conickx, Griet ;
Mesnil, Claire ;
Vandesompele, Jo ;
Lahousse, Lies ;
Bureau, Fabrice ;
Mestdagh, Pieter ;
Joos, Guy F. ;
Ricciardolo, Fabio L. M. ;
Brusselle, Guy G. ;
Louis, Renaud .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2016, 137 (05) :1433-1446
[39]   A MicroRNA Network Dysregulated in Asthma Controls IL-6 Production in Bronchial Epithelial Cells [J].
Martinez-Nunez, Rocio T. ;
Bondanese, Victor P. ;
Louafi, Fethi ;
Francisco-Garcia, Ana S. ;
Rupani, Hitasha ;
Bedke, Nicole ;
Holgate, Stephen ;
Howarth, Peter H. ;
Davies, Donna E. ;
Sanchez-Elsner, Tilman .
PLOS ONE, 2014, 9 (10)
[40]   The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor α1 (IL13Rα1) [J].
Martinez-Nunez, Rocio T. ;
Louafi, Fethi ;
Sanchez-Elsner, Tilman .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (03) :1786-1794