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Mohammed Aref Kyyaly
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Lindsay Dong
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Kyyaly, M.A.; Vorobeva, E.V.; Kothalawala, D.; , .; He, P.; Sanchez-Elsner, T.; Arshad, S.H.; Kurukulaaratchy, R. MicroRNAs in Asthma Diagnosis and Severity Assessment. Encyclopedia. Available online: https://encyclopedia.pub/entry/22789 (accessed on 15 June 2025).
Kyyaly MA, Vorobeva EV, Kothalawala D,  , He P, Sanchez-Elsner T, et al. MicroRNAs in Asthma Diagnosis and Severity Assessment. Encyclopedia. Available at: https://encyclopedia.pub/entry/22789. Accessed June 15, 2025.
Kyyaly, Mohammed Aref, Elena Vladimirovna Vorobeva, Dilini Kothalawala,  , Peijun He, Tilman Sanchez-Elsner, S. Hasan Arshad, Ramesh Kurukulaaratchy. "MicroRNAs in Asthma Diagnosis and Severity Assessment" Encyclopedia, https://encyclopedia.pub/entry/22789 (accessed June 15, 2025).
Kyyaly, M.A., Vorobeva, E.V., Kothalawala, D., , ., He, P., Sanchez-Elsner, T., Arshad, S.H., & Kurukulaaratchy, R. (2022, May 10). MicroRNAs in Asthma Diagnosis and Severity Assessment. In Encyclopedia. https://encyclopedia.pub/entry/22789
Kyyaly, Mohammed Aref, et al. "MicroRNAs in Asthma Diagnosis and Severity Assessment." Encyclopedia. Web. 10 May, 2022.
MicroRNAs in Asthma Diagnosis and Severity Assessment
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This entry is adapted from the peer-reviewed paper 10.3390/jpm12040543

Micro RNAs (miRNAs) are short, non-coding RNAs (Ribonucleic acids) with regulatory functions that could prove useful as biomarkers for asthma diagnosis and asthma severity-risk stratification. 

asthma asthma severity biomarker diagnosis micro RNA

1. Introduction

Asthma is a high morbidity chronic condition affecting over 300 million people worldwide and causing 461,000 deaths globally in 2019 [1]. This global disease burden is expected to rise to 400 million cases by 2025 [2]. It is recognised that asthma is a heterogeneous state composed of numerous clinical phenotypes which may have different underlying biological pathways. Given the absence of gold standard tests to diagnose asthma, most guidelines concur that asthma remains a clinical diagnosis. However, such diagnostic approaches are open to subjective variation. Severe asthma is defined by ATS (American Thoracic Society)/ERS (European Respiratory Society) guidelines as asthma requiring treatment with high-dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or that remains ‘‘uncontrolled’’ despite this therapy [3]. It places a significant burden on both individual patients and wider healthcare resources. There is a clear need to develop diagnostic biomarkers both to aid asthma diagnosis and identify phenotypes with a higher severity risk [4][5].
MicroRNAs (miRNAs) are small non-coding RNAs (Ribonucleic acids), 22–25 nucleotides long, acting through RNA-induced silencing complexes to post-transcriptionally regulate mRNAs (messenger RNA) containing complementary sequences. Highly stable circulating miRNAs occur in biological fluids including peripheral blood and are potential biomarkers [6][7] for diagnosis, prognosis, and disease monitoring [8]. Growing evidence indicates that miRNAs are differentially expressed in asthmatics compared to non-asthmatics and have immunoregulatory effects [9][10][11][12][13][14]. Differences in both exhaled breath condensate (EBC) and bronchoalveolar lavage (BAL) fluid miRNA profiles occur in asthmatics compared to healthy controls. miR-570-3p has shown diverse effects on cytokine expression in human airway epithelial cells while serum and EBC levels correlate inversely with lung function [15].
A set of miRNAs assessed in blood were recently reported and could classify asthmatics into two clusters by blood eosinophil numbers and periostin concentration [16]. Differential serum expression has also been shown between asthma and Chronic Obstructive Pulmonary Disease for multiple miRNAs [17].
Given presence and stability in various tissues, miRNAs are attractive potential biomarkers to aid in the diagnosis of asthma, identification of distinct asthma phenotypes, and stratification of asthma severity-risk.

2. MicroRNAs in Asthma Diagnosis and Severity Assessment

miR-146a was found to be of diagnostic value for asthma as it was upregulated in the blood of asthmatics and associated with markers of poor asthma control, such as the Asthma Control Questionnaire score [18]. Expression of this miRNA was also found to inhibit the proliferation and promote the apoptosis of Bronchial Smooth Muscle Cells, providing a novel clinical marker for the diagnosis and stratification of asthma [19].
A role of miR-30a in suppressing airway fibrosis and autophagy by targeting ATG5 (autophagy-related gene 5) has been shown [20]. Thus, miR-30a expression inversely correlates with autophagy in asthma, supporting the hypothesis that lower miR-30a levels lead to the overexpression of ATG5, which promotes asthma progression. Conversely, increased miR-21 expression has been previously associated with asthma development, mainly due to its targeting of IL-12p35 highlighting the multi-functional roles of miRNAs in several cell types contributing synergistically to asthma pathology [21]. Functionally, miRNA-21 can stimulate a Th2 response by two different mechanisms [22]. The first mechanism is mediated by the ability of miRNA-21 to inhibit IL-12 gene expression, resulting in the inhibition of Th1 functions, including the decreased release of IFN-γ. Low IFN-γ levels lead to unrestricted Th2 activation and elevated Th2 cytokines. Th2 cytokines can additionally augment miRNA-21-mediated responses [23]. Second, miRNA-21 can directly induce differentiation of T cells towards Th2 lineage by escalating GATA-3 and IL-4 expression immediately after T-cell activation [24][25][26].
Three miRNAs miR-155, miR-126, and miR-125b were shared between the two panels and will be discussed further. These miRNAs are thought to be influential in miR-mediated Toll-like receptor (TLR) signalling and cytokine signalling in asthma [27].
miR-155 is one of the most studied miRNAs. It is implicated in a variety of diseases and is widely studied in asthma [28]. miR-155 is a critical regulator of type 2 innate lymphoid cells in murine models of allergic airway inflammation [29] and was shown to be differentially expressed in the airways of allergic asthmatic individuals compared to healthy controls [30]. It was also found that the increased expression of miR-155 enhances mucus secretion and regulates the secretion of IL-4, IL-5, IL-13, and IL-17a [31][32].
A recent study found a highly significant correlation between the increased expression of miR-125b and CRP/IgE levels (r = 0.86/r = 0.68; p < 0.0001) in asthma patients, indicating the potential relevance of this miRNA for particular asthma phenotypes.
It has been reported [33] that the overexpression of miR-126 in bronchial epithelial cells can promote increased levels of the Th2 cytokine IL-13, suggesting that miR-126 should be studied as a factor related to the excessive activation of Th2 cells in asthmatic children. It has been also found that the relative level of miR-126 was independently associated with the proportion of Th17 cells, indicating that the mechanism of miR-126 overexpression in promoting asthma may also be related to the proportion of Th17 cells. The same study [33] also showed that the relative level of miR-126 in the peripheral blood of asthma children was associated with the degree of asthma severity, emphasising its potential role as a severity risk marker.
One noteworthy finding was that some miRNAs can be upregulated in one tissue compartment but downregulated in another compartment. For example, miR-155 is upregulated in serum and downregulated everywhere else (BAL, sputum, and nasal biopsies) [30][34][35][36]. This differential downregulation suggests that some miRNAs can be used as a biomarker but that scholars cannot yet necessarily draw functional conclusions about their role in asthma pathophysiology or clinical expression.
Despite the increasing evidence that miRNAs play important roles in asthma, the studies performed so far were mostly conducted in in vitro or animal models of asthma, and evidence in humans remains limited. Thus, adequately powered studies are now needed to improve the insight into the role of miRNAs in relevant human cells and tissues [37]. Further studies to assess the clinical utility of such diagnostic and severity-risk miRNA panels in asthma as well as functional roles of those miRNAs in the pathogenesis and clinical expression of asthma should be a future research focus.

References

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  15. Roff, A.N.; Craig, T.J.; August, A.; Stellato, C.; Ishmael, F.T. MicroRNA-570-3p regulates HuR and cytokine expression in airway epithelial cells. Am. J. Clin. Exp. Immunol. 2014, 3, 68–83.
  16. Rodrigo-Muñoz, J.M.; Cañas, J.A.; Sastre, B.; Rego, N.; Greif, G.; Rial, M.; Mínguez, P.; Mahíllo-Fernández, I.; Fernández-Nieto, M.; Mora, I.; et al. Asthma diagnosis using integrated analysis of eosinophil microRNAs. Allergy 2018, 74, 507–517.
  17. Wang, M.; Huang, Y.; Liang, Z.; Liu, D.; Lu, Y.; Dai, Y.; Feng, G.; Wang, C. Plasma miRNAs might be promising biomarkers of chronic obstructive pulmonary disease. Clin. Respir. J. 2016, 10, 104–111.
  18. Lambert, K.A.; Roff, A.N.; Panganiban, R.P.; Douglas, S.; Ishmael, F.T. MicroRNA-146a is induced by inflammatory stimuli in airway epithelial cells and augments the anti-inflammatory effects of glucocorticoids. PLoS ONE 2018, 13, e0205434.
  19. Zhang, Y.; Xue, Y.; Liu, Y.; Song, G.; Lv, G.; Wang, Y.; Wang, Y.; Li, X.; Yang, L. MicroRNA-146a expression inhibits the proliferation and promotes the apoptosis of bronchial smooth muscle cells in asthma by directly targeting the epidermal growth factor receptor. Exp. Ther. Med. 2016, 12, 854–858.
  20. Bin Li, B.; Chen, Y.L.; Pang, F. MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy. Inflammation 2019, 43, 44–53.
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  23. Lu, T.X.; Hartner, J.; Lim, E.J.; Fabry, V.; Mingler, M.K.; Cole, E.T.; Orkin, S.H.; Aronow, B.J.; Rothenberg, M.E. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J. Immunol. 2011, 187, 3362–3373.
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Subjects: Allergy
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Mohammed Aref Kyyaly
,
Elena Vladimirovna Vorobeva
,
Dilini Kothalawala
,
,
Peijun He
,
Tilman Sanchez-Elsner
,
S. Hasan Arshad
,
Ramesh Kurukulaaratchy
View Times: 540
Revisions: 2 times (View History)
Update Date: 13 May 2022
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