Peripheral Blood Expressions of MicroRNA-146a and MicroRNA-218 in Chronic Obstructive Pulmonary Disease with/without Cigarette Smoke Exposure
Abstract
Altered expression and dysregulation of microRNAs (miRNAs) have been reported in different samples of chronic obstructive pulmonary disease (COPD) patients. The present study attempted to evaluate the peripheral expressions of miR-146a and miR-218 in COPD patients and sex-matched healthy controls with/without cigarette smoke exposure (CSE).
In this case-control study, blood samples were collected from 60 COPD patients (30 with CSE and 30 non-CSE in each group) and 60 healthy controls. Peripheral expressions of miRNA-146a and miR-218a were measured using qRT-PCR and results were compared between cases and controls as well as within the subgroups of patients.
We found significantly decreased expressions for both miRNAs in the patients compared to healthy controls. Remarkable underexpression of miRNA-146a and miRNA-218 were found in the CSE and non-CSE patients compared to non-CSE healthy controls and even in the CSE versus non-CSE controls. Both groups of patients showed underexpression of two miRNAs in comparison with CSE healthy controls and interestingly, similar decrements were observed in the CSE versus non-CSE patients. Also, ROC curve analysis revealed the significantly diagnostic powers for both miRNAs in discrimination of patients from healthy individuals and CSE-COPD from non-CSE COPD patients.
The underexpression of miR-146a and miR-218 in COPD patients and relation to CSE can be indicative of CSE-induced changes in miRNA expression profile and potential for these biomarkers in COPD risk assessment, particularly in those patients with CSE.
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25. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–6.
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28. Profita M, Sala A, Bonanno A, Riccobono L, Ferraro M, La Grutta S, et al. Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products. Am J Physiol Lung Cell Mol Physiol. 2010;298(2):1261–9.
29. Huang SK, Wettlaufer SH, Chung J, Peters-Golden M. Prostaglandin E2 inhibits specific lung fibroblast functions via selective actions of PKA and Epac-1. Am J Respir Cell Mol Biol. 2008;39(4):482–9.
30. Tan BWQ, Sim WL, Cheong JK, Kuan WS, Tran T, Lim HF. MicroRNAs in chronic airway diseases: Clinical correlation and translational applications. Pharmacol Res. 2020;160(8):105045-9.
31. De Smet EG, Mestdagh P, Vandesompele J, Brusselle GG, Bracke KR. Non-coding RNAs in the pathogenesis of COPD. Thorax. 2015;70(8):782-91.
32. Molina-Pinelo S, Pastor MD, Suarez R, Romero-Romero B, González De la Peña M, Salinas A, et al. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. Eur Respir J. 2014;43(6):1740–9.
33. Izzotti A, Larghero P, Longobardi M, Cartiglia C, Camoirano A, Steele VE, et al. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung. Mutat Res. 2011;717(1-2):9–16.
34. Liu X, Wang J, Luo H, Xu C, Chen X, Zhang R. MiR-218 Inhibits CSE-Induced Apoptosis and Inflammation in BEAS-2B by Targeting BRD4. Int J Chron Obstruct Pulmon Dis. 2020;15(2):3407-9.
35. Conickx G, Mestdagh P, Avila Cobos F, Verhamme FM, Maes T, Vanaudenaerde BM, et al. MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195(1):43-56.
36. Song J, Wang Q, Zou S. Role of microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2018;22(13):4319-24.
2. Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Annu Rev Pathol. 2009;4(1):435–59.
3. Løkke A, Lange P, Vestbo J, Fabricius PG. Developing COPD – 25 years follow-up study of the general population. Ugeskr Laeg. 2006;168(50):4422–4.
4. Sakao S, Tatsumi K. The importance of epigenetics in the development of chronic obstructive pulmonary disease. Respirology. 2011;16(7):1056–63.
5. Osei ET, Florez-Sampedro L, Timens W, Postma DS, Heijink IH, Brandsma CA. Unravelling the complexity of COPD by microRNAs: it’s a small world after all. Eur Respir J. 2015;46(3):807–18.
6. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15(11):509-24.
7. Van Pottelberge GR, Mestdagh P, Bracke KR, Thas O, van Durme YM, Joos GF, 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.
8. Bossé Y, Postma DS, Sin DD, Lamontagne M, Couture C, Gaudreault N, et al. Molecular signature of smoking in human lung tissues. Cancer Res. 2012;72(15):3753–63.
9. Akbas F, Coskunpinar E, Aynaci E, Oltulu YM, Yildiz P. Analysis of serum micro-RNAs as potential biomarker in chronic obstructive pulmonary disease. Exp Lung Res 2012;38(6):286-94.
10. Conickx G, Avila Cobos F, van den Berge M, Faiz A, Timens W, Hiemstra PS, et al. microRNA profiling in lung tissue and bronchoalveolar lavage of cigarette smoke-exposed mice and in COPD patients: a translational approach. Sci Rep. 2017;7(1):12871-8.
11. Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N, Wang X, et al. Reduced miR-146a increases prostaglandin E2 in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med. 2010;182(8):1020–9.
12. Churov AV, Oleinik EK, Knip M. MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev. 2015;14(11):1029–37.
13. Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2010;12(3):R86.
14. Hassan T, Carroll TP, Buckley PG, Cummins R, O'Neill SJ, McElvaney NG, et al. miR-199a-5p silencing regulates the unfolded protein response in chronic obstructive pulmonary disease and alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2014;189(3):263-73.
15. Dang X, Qu X, Wang W, Liao C, Li Y, Zhang X, et al. Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease. Respir Res. 2017;18(1):1-13.
16. Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S, Gelinas R, et al. Gene expression networks in COPD: microRNA and mRNA regulation. Thorax. 2012;67(2):122–31.
17. Hassan F, Nuovo GJ, Crawford M, Boyaka PN, Kirkby S, Nana-Sinkam SP, et al. MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung. PLoS One. 2012;7(11): e50837.
18. Mizuno S, Bogaard HJ, Gomez-Arroyo J, Alhussaini A, Kraskauskas D, Cool CD, et al. MicroRNA-199a-5p is associated with hypoxia-inducible factor-1alpha expression in lungs from patients with COPD. Chest. 2012;142(3):663–72.
19. Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, et al. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci USA. 2009;106(7):2319–24.
20. http://www.cdc.gov/nchc/nhis/tobacco/tobacco_glosaary.
21 Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101-8.
22. Sheedy FJ and O’Neill LA. Adding fuel to fire: microRNAs as a new class of mediators of inflammation. Ann Rheum Dis. 2008;(67 Suppl 3):50-5.
23. Rusca N, Monticelli S. MiR-146a in immunity and disease. Mol Biol Int. 2011;2011:437301.
24. Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA. Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett. 2009; 583(20):3349–55.
25. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 2006;103(33):12481–6.
26. Martey CA, Pollock SJ, Turner CK, O'Reilly KM, Baglole CJ, Phipps RP, et al. Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer. Am J Physiol Lung Cell Mol Physiol. 2004;287(5):L981–91.
27. Montuschi P, Kharitonov SA, Ciabattoni G, Barnes PJ. Exhaled leukotrienes and prostaglandins in COPD. Thorax. 2003;58(7):585–8.
28. Profita M, Sala A, Bonanno A, Riccobono L, Ferraro M, La Grutta S, et al. Chronic obstructive pulmonary disease and neutrophil infiltration: role of cigarette smoke and cyclooxygenase products. Am J Physiol Lung Cell Mol Physiol. 2010;298(2):1261–9.
29. Huang SK, Wettlaufer SH, Chung J, Peters-Golden M. Prostaglandin E2 inhibits specific lung fibroblast functions via selective actions of PKA and Epac-1. Am J Respir Cell Mol Biol. 2008;39(4):482–9.
30. Tan BWQ, Sim WL, Cheong JK, Kuan WS, Tran T, Lim HF. MicroRNAs in chronic airway diseases: Clinical correlation and translational applications. Pharmacol Res. 2020;160(8):105045-9.
31. De Smet EG, Mestdagh P, Vandesompele J, Brusselle GG, Bracke KR. Non-coding RNAs in the pathogenesis of COPD. Thorax. 2015;70(8):782-91.
32. Molina-Pinelo S, Pastor MD, Suarez R, Romero-Romero B, González De la Peña M, Salinas A, et al. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. Eur Respir J. 2014;43(6):1740–9.
33. Izzotti A, Larghero P, Longobardi M, Cartiglia C, Camoirano A, Steele VE, et al. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung. Mutat Res. 2011;717(1-2):9–16.
34. Liu X, Wang J, Luo H, Xu C, Chen X, Zhang R. MiR-218 Inhibits CSE-Induced Apoptosis and Inflammation in BEAS-2B by Targeting BRD4. Int J Chron Obstruct Pulmon Dis. 2020;15(2):3407-9.
35. Conickx G, Mestdagh P, Avila Cobos F, Verhamme FM, Maes T, Vanaudenaerde BM, et al. MicroRNA profiling reveals a role for microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2017;195(1):43-56.
36. Song J, Wang Q, Zou S. Role of microRNA-218-5p in the pathogenesis of chronic obstructive pulmonary disease. Eur Rev Med Pharmacol Sci. 2018;22(13):4319-24.
| Files | ||
| Issue | Vol 21 No 4 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i4.10287 | |
| Keywords | ||
| Chronic obstructive pulmonary disease Smoking | ||
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How to Cite
1.
Nadi E, Geramirad G, Kahramfar Z, Rasuli-Saravani A, Solgi G. Peripheral Blood Expressions of MicroRNA-146a and MicroRNA-218 in Chronic Obstructive Pulmonary Disease with/without Cigarette Smoke Exposure. Iran J Allergy Asthma Immunol. 2022;21(4):399-406.
