Research Article

The Plasma Levels of hsa-miR-19b-3p, hsa-miR-125b-5p, and hsamiR- 320c in Patients with Asthma, COPD and Asthma-COPD Overlap Syndrome (ACOS)

Author(s): Rakhmetkazhy Bersimbaev*, Akmaral Aripova*, Olga Bulgakova, Аssya Kussainova , Almira Akparova and Alberto Izzotti

Volume 10 , Issue 2 , 2021

Published on: 09 June, 2021

Page: [130 - 138] Pages: 9

DOI: 10.2174/2211536610666210609142859

Price: $65


Background: Bronchial Asthma (BA) and Chronic Obstructive Pulmonary Disease (COPD) are chronic airway inflammation diseases. In recent years, patients with signs of both BA and COPD have been assigned to a separate group as Asthma-COPD Overlap Syndrome (ACOS). Free-circulating plasma microRNAs are considered as potential biomarkers of pulmonology diseases, including BA, COPD, and ACOS.

Objective: This study aimed to investigate the expression level of free-circulating plasma microRNAs, hsa-miR-19b-3p, hsa-miR-125b-5p, and hsa-miR-320c in patients with BA, COPD and ACOS for the detection and validation of new microRNAs as biomarkers for chronic lung diseases.

Methods: The relative expression levels of 720 microRNAs were evaluated by Real Time-Polymerase Chain Reaction (RT-PCR) in patients with COPD and BA. Three upregulated microRNAs (hsa-miR-19b-3p, hsa-miR-125b-5p and hsa-miR-320c) were selected for further study. The obtained data were analyzed using the microRNA PCR Array Data Analysis tool. The sensitivity and specificity were estimated using the area under the Receiver Operating Characteristics curve (ROC).

Results: The expression level of free-circulating hsa-miR-19b-3p was decreased in the blood plasma of patients with BA and ACOS, and increased in patients with COPD. hsa-miR-125b-5p was downregulated in the blood plasma of patients with COPD and upregulated in patients with BA and ACOS. hsa-miR-320c was downregulated in the blood plasma of patients with BA, and upregulated in patients with COPD and ACOS. The ROC curves of patients with BA for hsa-miR-19b-3p, patients with ACOS for hsa-miR-125b-5p, and patients with COPD for hsa-miR-320c revealed the probability of them as valuable biomarkers with AUCs of 0.824, 0.825, and 0.855, respectively.

Conclusion: Our study revealed three promising biomarkers for the diagnosis of COPD, BA and ACOS.

Keywords: Circulating hsa-miR-19b-3p, hsa-miR-320c, hsa-miR-125b-5p, bronchial asthma, chronic obstructive pulmonary disease, Asthma-COPD Overlap Syndrome (ACOS).

Graphical Abstract
Yanagisawa S, Ichinose M. Definition and diagnosis of Asthma-COPD Overlap (ACO). Allergol Int 2018; 67(2): 172-8.
[] [PMID: 29433946]
Nielsen M, Bårnes CB, Ulrik CS. Clinical characteristics of the asthma-COPD overlap syndrome - A systematic review. Int J Chron Obstruct Pulmon Dis 2015; 10: 1443-54.
[PMID: 26251584]
Roche N, Chavannes NH, Miravitlles M. COPD symptoms in the morning: Impact, evaluation and management. Respir Res 2013; 14(1): 112.
[] [PMID: 24143997]
Szymczak I, Wieczfinska J, Pawliczak R. Molecular background of miRNA role in asthma and COPD: An updated insight. BioMed Res Int 2016; 2016: 7802521.
[] [PMID: 27376086]
Lacedonia D, Palladino GP, Foschino-Barbaro MP, Scioscia G, Carpagnano GE. Expression profiling of miRNA-145 and miRNA-338 in serum and sputum of patients with COPD, asthma, and asthma-COPD overlap syndrome phenotype. Int J Chron Obstruct Pulmon Dis 2017; 12: 1811-7.
[] [PMID: 28694694]
Tsai MJ, Tsai YC, Chang WA, et al. Deducting microRNA-mediated changes common in bronchial epithelial cells of asthma and chronic obstructive pulmonary disease-A next-generation sequencing-guided bioinformatic approach. Int J Mol Sci 2019; 20(3): 553.
[] [PMID: 30696075]
Huang X, Zhu Z, Guo X, Kong X. The roles of microRNAs in the pathogenesis of chronic obstructive pulmonary disease. Int Immunopharmacol 2019; 67: 335-47.
[] [PMID: 30578969]
Stolzenburg LR, Harris A. The role of microRNAs in chronic respiratory disease: Recent insights. Biol Chem 2018; 399(3): 219-34.
[] [PMID: 29148977]
Pepin G, Gantier MP. MicroRNA decay: Refining microRNA regulatory activity. MicroRNA 2016; 5(3): 167-74.
[] [PMID: 27804865]
Wang Y, Wang L, Chen C, Chu X. New insights into the regulatory role of microRNA in tumor angiogenesis and clinical implications. Mol Cancer 2018; 17(1): 22.
[] [PMID: 29415727]
Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: How many mechanisms? Trends Cell Biol 2007; 17(3): 118-26.
[] [PMID: 17197185]
Chan B, Manley J, Lee J, Singh SR. The emerging roles of microRNAs in cancer metabolism. Cancer Lett 2015; 356(2): 301-8.
[] [PMID: 25451319]
Li M, Dong Y, Chen Z, et al. MicroRNA-31 negatively regulates interleukin-34 expression in vitro. Immunol Invest 2019; 48(6): 597-607.
[] [PMID: 31012336]
Wang JW, Li K, Hellermann G, Lockey RF, Mohapatra S, Mohapatra S. Regulating the regulators: MicroRNA and asthma. World Allergy Organ J 2011; 4(6): 94-103.
[] [PMID: 23282474]
Svitich OA, Sobolev VV, Gankovskaya LV, Zhigalkina PV, Zverev VV. The role of regulatory RNAs (miRNAs) in asthma. Allergol Immunopathol (Madr) 2018; 46(2): 201-5.
[] [PMID: 29342408]
Kilgour E, Rothwell DG, Brady G, Dive C. Liquid biopsy-based biomarkers of treatment response and resistance. Cancer Cell 2020; 37(4): 485-95.
[] [PMID: 32289272]
Mosleh LA. Genetics in oncology, liquid biopsy and circulating tumor DNA. Journal of Cancer Science & Therapy OMICS Publishing Group 2017; 09(01)
Garcia CM, Toms SA. The role of circulating microRNA in Glioblastoma liquid biopsy. World Neurosurg 2020; 138: 425-35.
[] [PMID: 32251831]
Sato T, Baskoro H, Rennard SI, Seyama K, Takahashi K. MicroRNAs as therapeutic targets in lung disease: Prospects and challenges. Chronic Obstr Pulm Dis (Miami) 2015; 3(1): 382-8.
[] [PMID: 28848860]
Members of GINA Committees. Global strategy for asthma management and prevention; global initiative for asthma. Fontana. GINA 2019. Available from:
GOLD Science Committee Members. Global strategy for diagnosis, management, and prevention of COPD 2018. Global initiative for obstructive lung disease. Available from: (Accessed on 28 January 2019).
Kaneko Y, Yatagai Y, Yamada H, et al. The search for common pathways underlying asthma and COPD. Int J Chron Obstruct Pulmon Dis 2013; 8: 65-78.
[PMID: 23378757]
He L, Thomson JM, Hemann MT, et al. A microRNA polycistron as a potential human oncogene. Nature 2005; 435(7043): 828-33.
[] [PMID: 15944707]
Ventura A, Young AG, Winslow MM, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell 2008; 132(5): 875-86.
[] [PMID: 18329372]
Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol 2007; 310(2): 442-53.
[] [PMID: 17765889]
McKiernan PJ, Smith SGJ, Durham AL, Adcock IM, McElvaney NG, Greene CM. The estrogen-induced miR-19 downregulates secretory leucoprotease inhibitor expression in monocytes. J Innate Immun 2020; 12(1): 90-102.
[] [PMID: 31266011]
Simpson LJ, Patel S, Bhakta NR, et al. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production. Nat Immunol 2014; 15(12): 1162-70.
[] [PMID: 25362490]
Rao E, Jiang C, Ji M, et al. The miRNA-17∼92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation. Leukemia 2012; 26(5): 1064-72.
[] [PMID: 22116552]
Dews M, Fox JL, Hultine S, et al. The myc-miR-17~92 axis blunts TGFbeta signaling and production of multiple TGFbeta-dependent antiangiogenic factors. Cancer Res 2010; 70(20): 8233-46.
[] [PMID: 20940405]
Molina-Pinelo S, Pastor MD, Suarez R, et al. MicroRNA clusters: Dysregulation in lung adenocarcinoma and COPD. Eur Respir J 2014; 43(6): 1740-9.
[] [PMID: 24743967]
Zhao L, Feng Y, Lu J, Gu X, Li Q. Mechanism of LncRNA-ICL in chronic obstructive pulmonary disease progressing to lung cancer. In: B63 exploring COPD by marker, mechanism, and signatures Am Thorac Soc. 201: 4013.
Atlas of Genetics and Cytogenetics in Oncology and Haematology. Available from:
Glasson SS, Chambers MG, Van Den Berg WB, Little CB. The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage 2010; 18(3): S17-23.
[] [PMID: 20864019]
Ukai T, Sato M, Akutsu H, Umezawa A, Mochida J. MicroRNA-199a-3p, microRNA-193b, and microRNA-320c are correlated to aging and regulate human cartilage metabolism. J Orthop Res 2012; 30(12): 1915-22.
[] [PMID: 22674437]
Hamam D, Ali D, Vishnubalaji R, et al. MicroRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells. Cell Death Dis 2014; 5(10): e1499.
[] [PMID: 25356868]
Lv QL, Zhu HT, Li HM, Cheng XH, Zhou HH, Chen SH. Down-regulation of miRNA-320c promotes tumor growth and metastasis and predicts poor prognosis in human glioma. Brain Res Bull 2018; 139: 125-32.
[] [PMID: 29438779]
Matamala N, Lara B, Gómez-Mariano G, et al. MiR-320c regulates SERPINA1 expression and is induced in patients with pulmonary disease. Arch Bronconeumol 2020; 57(7): 457-63.
DeMeo DL, Silverman EK. Alpha1-antitrypsin deficiency. 2: Genetic aspects of alpha(1)-antitrypsin deficiency: Phenotypes and genetic modifiers of emphysema risk. Thorax 2004; 59(3): 259-64.
[] [PMID: 14985567]
Hassan T, Smith SG, Gaughan K, et al. Isolation and identification of cell-specific microRNAs targeting a messenger RNA using a biotinylated anti-sense oligonucleotide capture affinity technique. Nucleic Acids Res 2013; 41(6): e71.
[] [PMID: 23325846]
Keller A, Fehlmann T, Ludwig N, et al. Genome-wide microRNA expression profiles in COPD: Early predictors for cancer development. Genomics Proteomics Bioinformatics 2018; 16(3): 162-71.
[] [PMID: 29981854]
Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli S. MiR-125 in normal and malignant hematopoiesis. Leukemia 2012; 26(9): 2011-8.
[] [PMID: 22456625]
Zhao M, Juanjuan L, Weijia F, et al. Expression levels of microRNA-125b in serum exosomes of patients with asthma of different severity and its diagnostic significance. Curr Drug Metab 2019; 20(10): 781-4.
[] [PMID: 31631818]
Specjalski K, Jassem E. MicroRNAs: Potential biomarkers and targets of therapy in allergic diseases? Arch Immunol Ther Exp (Warsz) 2019; 67(4): 213-23.
[] [PMID: 31139837]
Panganiban RP, Wang Y, Howrylak J, et al. Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma. J Allergy Clin Immunol 2016; 137(5): 1423-32.
[] [PMID: 27025347]
Feketea G, Bocsan CI, Popescu C, Gaman M, Stanciu LA, Zdrenghea MT. A review of macrophage microRNAs’ role in human asthma. Cells 2019; 8(5): 420.
[] [PMID: 31071965]
Saluja R, Kumar A, Jain M, Goel SK, Jain A. Role of sphingosine-1-phosphate in mast cell functions and asthma and its regulation by non-coding RNA. Front Immunol 2017; 8: 587.
[] [PMID: 28588581]
Van Pottelberge GR, Mestdagh P, Bracke KR, et al. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2011; 183(7): 898-906.
[] [PMID: 21037022]
Le MT, Shyh-Chang N, Khaw SL, et al. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet 2011; 7(9): e1002242.
[] [PMID: 21935352]
Quinn EM, Wang J, Redmond HP. The emerging role of microRNA in regulation of endotoxin tolerance. J Leukoc Biol 2012; 91(5): 721-7.
[] [PMID: 22389313]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy