Original Article

Exosomal MicroRNAs as Biomarkers in Allergic Asthma

Exosomal MiRNAs in Asthma


Exosomes are extracellular vesicles that are involved in intracellular communication and different biological processes. Recently, the importance of microRNAs (miRNAs) in exosomes has been considered as biomarkers in asthma diagnosis. This study aimed to determine the expression of selective miRNAs from plasma-derived exosomes in moderate and severe asthmatic patients compared with healthy controls.
Forty-six subjects including 22 patients with severe and mild to moderate allergic asthma and 24 healthy controls have entered this study. MiRNAs were extracted from the plasma exosomes and selective miRNAs (miR-21, miR-16, miR-Let7, miR-148a, miR-155, miR-125, miR-150, miR-146a, miR-223, miR-126) expressions levels were determined; using quantitative polymerase chain reaction (qPCR).
In this study, we found a significant up-regulation of miR-223 and miR-21 in moderate asthmatic patients compared to the healthy controls (p=0.002, p=0.006). MiR-223 and miR-21 had the probability of 83% and 76% diagnosis estimation in moderate asthmatic patients respectively. Therefore, they could be used as biomarkers in these patients.  No expression of miR-125, miR-126, and miR-155 was found in plasma exosomes by qPCR in this study. The other miRNAs had no significant expression between different groups.
Based on our findings,miR-223 and miR-21 may be considered biomarkers or used for targeted immunotherapies in asthma.

1. Panganiban RP, Wang Y, Howrylak J, Chinchilli VM, Craig TJ, August A, et al. Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma.J Allergy Clin Immunol. 2016;137(5):1423-32.
2. Lobb RJ, Becker M, Wen Wen S, Wong CS, Wiegmans AP, Leimgruber A, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma.J Extracell Vesicles. 2015;4(1):27031.
3. Alipoor SD, Adcock IM, Garssen J, Mortaz E, Varahram M, Mirsaeidi M, et al. The roles of miRNAs as potential biomarkers in lung diseases.Eur J Pharmacol. 2016;791:395-404.
4. Heffler E, Allegra A, Pioggia G, Picardi G, Musolino C, Gangemi S. MicroRNA profiling in asthma: potential biomarkers and therapeutic targets.Am J Respir Cell Mol Biol. 2017;57(6):642-50.
5. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods. 2001;25(4):402-8.
6. RCore T. R: a language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria. 2015.
7. Hajian-Tilaki K. Receiver Operating Characteristic (ROC) Curve Analysis for Medical Diagnostic Test Evaluation. Caspian J Intern Med. 2013;4(2):627-35.
8. Agarwal V, Bell GW, Nam JW, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs.Elife. 2015;4.
9. Chou CH, Shrestha S, Yang CD, Chang NW, Lin YL, Liao KW, et al. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions. Nucleic Acids Res. 2018;46(D1):D296-d302.
10. Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451(7182):1125-9
11. Lu TX, Lim E-J, Besse JA, Itskovich S, Plassard AJ, Fulkerson PC, et al. MiR-223 deficiency increases eosinophil progenitor proliferation.J Immunol. 2013;190(4):1576-82.
12. Yuan X, Berg N, Lee JW, Le TT, Neudecker V, Jing N, et al. MicroRNA miR‐223 as regulator of innate immunity.J Leukoc Biol. 2018;104(3):515-24.
13. Maes T, Cobos FA, Schleich F, Sorbello V, Henket M, De Preter K, et al. Asthma inflammatory phenotypes show differential microRNA expression in sputum.J Allergy Clin Immunol.2016;137(5):1433-46.
14. Just J, Munk Ipsen P, Kruhoffer M, Lykkemark S, Skjold T, Schiotz PO, et al. Human Mast Cell Sensitization with IgE Increases miRNA-210 Expression. Int Arch Allergy Immunol. 2019;179(2):102-7.
15. Girodet P-O, Nguyen D, Mancini JD, Hundal M, Zhou X, Israel E, et al. Alternative macrophage activation is increased in asthma. Am J Respir Cell Mol Biol. 2016;55(4):467-75.
16. Hammad Mahmoud Hammad R, Hamed DHED, Eldosoky MAER, Ahmad AAES, Osman HM, Abd Elgalil HM, et al. Plasma microRNA-21, microRNA-146a and IL-13 expression in asthmatic children.Innate Immun. 2018;24(3):171-9.
17. Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression.J Immunol. 2009;182(8):4994-5002.
18. Weidner J, Malmhäll C, Rådinger M. MicroRNAs in asthma pathogenesis-from mouse to man. J Transl Genet Genom. 2019;3:2.
19. Kim RY, Horvat JC, Pinkerton JW, Starkey MR, Essilfie AT, Mayall JR, et al. MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2.J Allergy Clin Immunol. 2017;139(2):519-32.
20. Specjalski K, Jassem E. MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic Diseases?. Arch Immunol Ther Exp (Warsz).2019:1-11.
21. Han J, Zhao F, Zhang J, Zhu H, Ma H, Li X, et al. miR-223 reverses the resistance of EGFR-TKIs through IGF1R/PI3K/Akt signaling pathway.Int J Oncol. 2016;48(5):1855-67.
22. Jiang C, Guo Y, Yu H, Lu S, Meng L. Pleiotropic microRNA-21 in pulmonary remodeling: novel insights for molecular mechanism and present advancements. Allergy, asthma, and clinical immunology :J Allergy Clin Immunol. 2019;15:33.
23. Deepak B, Nahid A, Revai LE, Yizheng Y, Sarah A, Fengfeng B, et al. Simultaneous downregulation of miR-21 and upregulation of miR-7 has anti-tumor efficacy. Sci Rep. 2020;10(1).
24. Gavino A, Nahmod K, Bharadwaj U, Makedonas G, Tweardy D. STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model. Allergy. 2016;71(12):1684-92.
25. Fry RC, Rager JE, Bauer R, Sebastian E, Peden DB, Jaspers I, et al. Air toxics and epigenetic effects: ozone altered microRNAs in the sputum of human subjects.Am J Physiol Lung Cell Mol Physiol. 2014;306(12):L1129-L37.
IssueVol 20 No 2 (2021) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijaai.v20i2.6049
Asthma Exosomes MicroRNAs Plasma

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How to Cite
Rostami Hir S, Alizadeh Z, Mazinani M, Mahlooji Rad M, Fazlollahi MR, Kazemnejad A, Hosseini AZ, Moin M. Exosomal MicroRNAs as Biomarkers in Allergic Asthma. Iran J Allergy Asthma Immunol. 2021;20(2):160-168.