Circulating microRNAs correlate to clinical parameters in individuals with allergic and non-allergic asthma
Tóm tắt
Asthma is a chronic airway disease affecting millions of people. Better methods to define asthma subgroups using clinical parameters and molecular biomarkers are crucial in the development of personalized medicine. The aim of this study was to determine if circulating microRNAs (miRNAs) may be used to distinguish well–defined asthma groups. Blood serum from 116 well-defined subjects, including healthy controls and individuals with allergic or non-allergic asthma, from the West Sweden Asthma Study were included. Serum was analyzed for circulating miRNA expression of miR-126, − 145, −146a, − 155, − 223, and -374a and eosinophil cationic protein (ECP). Correlations between clinical characteristics and circulating miRNA expression as well as potential miRNA gene targets were investigated. A subset of miRNAs were differentially expressed between allergic and non-allergic asthmatic individuals. Alterations in expression of miR-155, −146a, −374a and − 145 were observed in allergic asthmatics in response to inhaled corticosteroid usage. Additionally, miR-223 and miR-374a expression varied in non-allergic asthmatics based on blood eosinophil numbers. Numerous clinical parameters, including lung function measurements, correlated with subsets of miRNAs. Finally, pathway analysis revealed a potential role for inhaled corticosteroid induced miRNAs in leukocyte regulation, IL-6 signaling and glucocorticoid response. Circulating miRNA expression was altered in subjects with allergic and non-allergic asthma and correlated to clinical parameters including lung function and potential gene targets involved in immune processes. This combination of clinical and molecular data may be a basis for the further, more precise classification of asthma subgroups. Taken together, these findings would further asthma research and benefit future patients through the discovery of molecular mechanisms as well as identifying asthma subgroups contributing to the development of personalized medicine.
Tài liệu tham khảo
GINA: Global strategy for asthma management and prevention. 2018.
Wenzel S. Severe asthma: from characteristics to phenotypes to endotypes. Clin Exp Allergy. 2012;42:650–8.
Ameis D, Khoshgoo N, Iwasiow BM, Snarr P, Keijzer R. MicroRNAs in lung development and disease. Paediatr Respir Rev. 2017;22:38–43.
Johansson K, Weidner J, Radinger M. MicroRNAs in type 2 immunity. Cancer Lett. 2018;425:116–24.
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1:15004.
Bartel DP. Metazoan MicroRNAs. Cell. 2018;173:20–51.
Gebert LFR, MacRae IJ. Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 2018.
Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2012;32:326–48.
O'Brien J, Hayder H, Zayed Y, Peng C. Overview of MicroRNA biogenesis, mechanisms of actions, and circulation. Front Endocrinol (Lausanne). 2018;9:402.
Davis JS, Sun M, Kho AT, Moore KG, Sylvia JM, Weiss ST, Lu Q, Tantisira KG. Circulating microRNAs and association with methacholine PC20 in the childhood asthma management program (CAMP) cohort. PLoS One. 2017;12:e0180329.
Kho AT, McGeachie MJ, Moore KG, Sylvia JM, Weiss ST, Tantisira KG. Circulating microRNAs and prediction of asthma exacerbation in childhood asthma. Respir Res. 2018;19:128.
Kho AT, Sharma S, Davis JS, Spina J, Howard D, McEnroy K, Moore K, Sylvia J, Qiu W, Weiss ST, Tantisira KG. Circulating MicroRNAs: association with lung function in asthma. PLoS One. 2016;11:e0157998.
Panganiban RP, Pinkerton MH, Maru SY, Jefferson SJ, Roff AN, Ishmael FT. Differential microRNA epression in asthma and the role of miR-1248 in regulation of IL-5. Am J Clin Exp Immunol. 2012;1:154–65.
Panganiban RP, Wang Y, Howrylak J, Chinchilli VM, Craig TJ, August A, Ishmael FT. Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma. J Allergy Clin Immunol. 2016;137:1423–32.
Callari M, Tiberio P, De Cecco L, Cavadini E, Dugo M, Ghimenti C, Daidone MG, Canevari S, Appierto V. Feasibility of circulating miRNA microarray analysis from archival plasma samples. Anal Biochem. 2013;437:123–5.
Ge Q, Zhou Y, Lu J, Bai Y, Xie X, Lu Z. miRNA in plasma exosome is stable under different storage conditions. Molecules. 2014;19:1568–75.
Grasedieck S, Scholer N, Bommer M, Niess JH, Tumani H, Rouhi A, Bloehdorn J, Liebisch P, Mertens D, Dohner H, et al. Impact of serum storage conditions on microRNA stability. Leukemia. 2012;26:2414–6.
Grasedieck S, Sorrentino A, Langer C, Buske C, Dohner H, Mertens D, Kuchenbauer F. Circulating microRNAs in hematological diseases: principles, challenges, and perspectives. Blood. 2013;121:4977–84.
Mraz M, Malinova K, Mayer J, Pospisilova S. MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun. 2009;390:1–4.
Lu TX, Lim EJ, Besse JA, Itskovich S, Plassard AJ, Fulkerson PC, Aronow BJ, Rothenberg ME. MiR-223 deficiency increases eosinophil progenitor proliferation. J Immunol. 2013;190:1576–82.
Mattes J, Collison A, Plank M, Phipps S, Foster PS. Antagonism of microRNA-126 suppresses the effector function of TH2 cells and the development of allergic airways disease. Proc Natl Acad Sci U S A. 2009;106:18704–9.
Collison A, Mattes J, Plank M, Foster PS. Inhibition of house dust mite-induced allergic airways disease by antagonism of microRNA-145 is comparable to glucocorticoid treatment. J Allergy Clin Immunol. 2011;128:160–7 e164.
Liu Y, Sun X, Wu Y, Fang P, Shi H, Xu J, Li M. Effects of miRNA-145 on airway smooth muscle cells function. Mol Cell Biochem. 2015;409:135–43.
Malmhall C, Johansson K, Winkler C, Alawieh S, Ekerljung L, Radinger M. Altered miR-155 expression in allergic asthmatic airways. Scand J Immunol. 2017;85:300–7.
Johansson K, Malmhall C, Ramos-Ramirez P, Radinger M. MicroRNA-155 is a critical regulator of type 2 innate lymphoid cells and IL-33 signaling in experimental models of allergic airway inflammation. J Allergy Clin Immunol. 2017;139:1007–16 e1009.
Malmhall C, Alawieh S, Lu Y, Sjostrand M, Bossios A, Eldh M, Radinger M: MicroRNA-155 is essential for T(H)2-mediated allergen-induced eosinophilic inflammation in the lung. J Allergy Clin Immunol 2014, 133:1429–1438, 1438 e1421–1427.
Milger K, Gotschke J, Krause L, Nathan P, Alessandrini F, Tufman A, Fischer R, Bartel S, Theis FJ, Behr J, et al. Identification of a plasma miRNA biomarker signature for allergic asthma: a translational approach. Allergy. 2017;72:1962–71.
Perry MM, Adcock IM, Chung KF. Role of microRNAs in allergic asthma: present and future. Curr Opin Allergy Clin Immunol. 2015;15:156–62.
Pua HH, Ansel KM. MicroRNA regulation of allergic inflammation and asthma. Curr Opin Immunol. 2015;36:101–8.
Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR, Hou L, Nguyen C, Solon M, Nguyen C, Barczak AJ, et al. Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med. 2012;186:965–74.
Weidner J, Malmhäll C, Rådinger M. microRNAs in asthma pathogenesis - from mouse to man. J Transl Genet Genom. 2019;3.
Daniel E, Roff A, Hsu MH, Panganiban R, Lambert K, Ishmael F. Effects of allergic stimulation and glucocorticoids on miR-155 in CD4(+) T-cells. Am J Clin Exp Immunol. 2018;7:57–66.
Dissanayake E, Inoue Y. MicroRNAs in allergic disease. Curr Allergy Asthma Rep. 2016;16:67.
Nwaru BI, Ekerljung L, Radinger M, Bjerg A, Mincheva R, Malmhall C, Axelsson M, Wennergren G, Lotvall J, Lundback B. Cohort profile: the West Sweden asthma study (WSAS): a multidisciplinary population-based longitudinal study of asthma, allergy and respiratory conditions in adults. BMJ Open. 2019;9:e027808.
Wong N, Wang X. miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res. 2015;43:D146–52.
Fan Y, Xia J. miRNet-functional analysis and visual exploration of miRNA-target interactions in a network context. Methods Mol Biol. 1819;2018:215–33.
Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, Huang WC, Sun TH, Tu SJ, Lee WH, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46:D296–302.
Venny. An interactive tool for comparing lists with Venn's diagrams. [http://bioinfogp.cnb.csic.es/tools/venny/index.html]. Accessed 20 June 2019.
Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–13.
Cain DW, Cidlowski JA. Immune regulation by glucocorticoids. Nat Rev Immunol. 2017;17:233–47.
Zhang S, Laryea Z, Panganiban R, Lambert K, Hsu D, Ishmael FT. Plasma microRNA profiles identify distinct clinical phenotypes in human asthmatics. J Trans Genet Genom. 2018;2.
Hammad Mahmoud Hammad R, Hamed D, Eldosoky M, Ahmad A, Osman HM, Abd Elgalil HM, Mahmoud Hassan MM. Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic children. Innate Immun. 2018;24:171–9.
Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, Franciosi JP, Putnam PE, Eby M, Martin LJ, et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012;129:1064–75 e1069.
Levanen B, Bhakta NR, Torregrosa Paredes P, Barbeau R, Hiltbrunner S, Pollack JL, Skold CM, Svartengren M, Grunewald J, Gabrielsson S, et al. Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients. J Allergy Clin Immunol. 2013;131:894–903.
Ilmarinen P, Tuomisto LE, Niemela O, Danielsson J, Haanpaa J, Kankaanranta T, Kankaanranta H. Comorbidities and elevated IL-6 associate with negative outcome in adult-onset asthma. Eur Respir J. 2016;48:1052–62.
Jevnikar Z, Ostling J, Ax E, Calven J, Thorn K, Israelsson E, Oberg L, Singhania A, Lau LCK, Wilson SJ, et al. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation. J Allergy Clin Immunol. 2019;143:577–90.
Yokoyama A, Kohno N, Fujino S, Hamada H, Inoue Y, Fujioka S, Ishida S, Hiwada K. Circulating interleukin-6 levels in patients with bronchial asthma. Am J Respir Crit Care Med. 1995;151:1354–8.
Rodrigo-Munoz JM, Canas JA, Sastre B, Rego N, Greif G, Rial M, Minguez P, Mahillo-Fernandez I, Fernandez-Nieto M, Mora I, et al. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy. 2019;74:507–17.