Severe Decline in Mir-20a and Mir-92a in the Context of the Mir-17-92 Cluster: Ideal Biomarkers of Various COPD Subtypes
Chronic obstructive pulmonary disease (COPD) is going to be the third leading cause of death by 2020. Circulating miRNAs are among the most beneficial feasible non-aggressive biomarkers for diagnosis and treatment of many diseases. Among members of the significant miR-17-92 cluster, miR-20a and miR-92a are greatly involved in both inflammation and hypoxia (known as the main reasons for COPD comorbidities). Thus, the expression of these miRNAs was evaluated in the serum of 26 patients and 19 controls using the sensitive stem-loop RT-qPCR approach. The results revealed a significant reduction of these miRNAs in patients relative to controls (P<0.001). Decreased expression of miR-20a in a patient might reflect a progressive stage of the disease. MiR-92a might be used as an early-detection biomarker of COPD. These miRNAs can be used as therapeutic targets specifically in the context of the miR-17-92 cluster to address the various clinicopathological aspects of the disease.
Akbas F, Coskunpinar E, Aynacı E, Müsteri Oltulu Y, Yildiz P 2012. Analysis of serum micro-RNAs as potential biomarker in chronic obstructive pulmonary disease. Experimental lung research, 38: 286-294.
Alipoor SD, Adcock IM, Garssen J, Mortaz E, Varahram M et al. 2016. The roles of miRNAs as potential biomarkers in lung diseases. European Journal of Pharmacology, 791: 395-404.
Almagro P, Soriano JB 2017. Underdiagnosis in COPD: a battle worth fighting. The Lancet Respiratory Medicine, 5: 367-368.
Alvanegh AG, Edalat H, Fallah P, Tavallaei M 2015. Decreased expression of miR-20a and miR-92a in the serum from sulfur mustard-exposed patients during the chronic phase of resulting illness. Inhalation toxicology, 27: 682-688.
Barnes PJ, Celli B 2009. Systemic manifestations and comorbidities of COPD. European Respiratory Journal, 33: 1165-1185.
Bartel DP 2009. MicroRNAs: target recognition and regulatory functions. Cell, 136: 215-233.
Brashier BB, Kodgule R 2013. Risk factors and pathophysiology of chronic obstructive pulmonary disease (COPD). J Assoc Physicians India, 60: 17-21.
Conickx G, FA Cobos, van den Berge M, Faiz A, Timens W et al. 2017. microRNA profiling in lung tissue and bronchoalveolar lavage of cigarette smoke-exposed mice and in COPD patients: a translational approach. Scientific reports, 7: 12871.
Croce CM, Calin GA 2005. miRNAs, cancer, and stem cell division. Cell, 122: 6-7.
Dakhlallah D, Batte K, Wang Y, Cantemir-Stone CZ, Yan P et al. 2013. Epigenetic regulation of miR-17∼ 92 contributes to the pathogenesis of pulmonary fibrosis. American journal of respiratory and critical care medicine, 187: 397-405.
Decramer M, Janssens W 2013. Chronic obstructive pulmonary disease and comorbidities. The Lancet Respiratory Medicine, 1: 73-83.
Guo L, Wang T, Wu Y, Yuan Z, Dong J et al. 2016. WNT/β-catenin signaling regulates cigarette smoke-induced airway inflammation via the PPARδ/p38 pathway. Laboratory investigation, 96: 218-229
Kelsen SG 2016. The unfolded protein response in chronic obstructive pulmonary disease. Annals of the American Thoracic Society, 13: S138-S145.
Lacedonia D, Palladino GP, Foschino-Barbaro MP, Scioscia G, Carpagnano GE 2017. Expression profiling of miRNA-145 and miRNA-338 in serum and sputum of patients with COPD, asthma, and asthma–COPD overlap syndrome phenotype. International journal of chronic obstructive pulmonary disease, 12: 1811-1817.
Leidinger P, Keller A, Borries A, Huwer H, Rohling M et al. 2011. Specific peripheral miRNA profiles for distinguishing lung cancer from COPD. Lung cancer, 74: 41-47.
Livak KJ, Schmittgen TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 25: 402-408.
Lu Y, Thomson JM, Wong HYF, Hammond SM, Hogan BL 2007. Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Developmental biology, 310: 442-453.
MacNee W 2005. Pathogenesis of chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society, 2: 258-266.
McGuinness AJA, Sapey E 2017. Oxidative Stress in COPD: Sources, Markers, and Potential Mechanisms. Journal of clinical medicine, 6: 21.
Mercer BA, D Armiento JM 2006. Emerging role of MAP kinase pathways as therapeutic targets in COPD. International journal of chronic obstructive pulmonary disease, 1: 137.
Mestdagh P, Feys T, Bernard N, Guenther S, Chen C et al. 2008. High-throughput stem-loop RT-qPCR miRNA expression profiling using minute amounts of input RNA. Nucleic acids research, 36: e143-e143.
Mogilyansky E, Rigoutsos I 2013. The miR-17/92 cluster: a comprehensive update on its genomics, genetics, functions and increasingly important and numerous roles in health and disease. Cell Death & Differentiation, 20: 1603-1614.
Molina-Pinelo S, Pastor MD, Suarez R, Romero-Romero B, De la Peña MG, et al. 2014. MicroRNA clusters: dysregulation in lung adenocarcinoma and COPD. European Respiratory Journal, 43: 1740-1749.
Najafi A, Masoudi-Nejad A, Ghanei M, Nourani M-R, Moeini A 2014. Pathway reconstruction of airway remodeling in chronic lung diseases: a systems biology approach. PLOS One, 9: e100094.
Nana-Sinkam SP, Karsies T, Riscili B, Ezzie M, Piper M 2009. Lung microRNA: from development to disease. Expert review of respiratory medicine, 3: 373-385.
Obeidat ME, Hao K, Bossé Y, Nickle DC, Nie Y et al. 2015. Molecular mechanisms underlying variations in lung function: a systems genetics analysis. The Lancet Respiratory Medicine, 3: 782-795.
Osei ET, Florez-Sampedro L, Timens W, Postma DS, Heijink IH, Brandsma C-A 2015. Unravelling the complexity of COPD by microRNAs: it's a small world after all. European Respiratory Journal, 46: 807-18
Poitz DM, Augstein A, Gradehand C, Ende G, Schmeisser A, Strasser RH 2013. Regulation of the Hif-system by micro-RNA 17 and 20a–role during monocyte-to-macrophage differentiation. Molecular immunology, 56: 442-451.
Raherison C, Girodet P 2009. Epidemiology of COPD. European Respiratory Review, 18: 213-221.
Schamberger AC, Mise N, Meiners S, Eickelberg O 2014. Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery. Expert opinion on drug discovery, 9: 609-628.
Shimoda LA, Semenza GL 2011. HIF and the lung: role of hypoxia-inducible factors in pulmonary development and disease. American journal of respiratory and critical care medicine, 183: 152-156.
Sng JJ, Prazakova S, Thomas PS, Herbert C 2017. MMP-8, MMP-9 and Neutrophil Elastase in Peripheral Blood and Exhaled Breath Condensate in COPD. COPD: Journal of Chronic Obstructive Pulmonary Disease, 14: 238-244.
Sundar IK, Yao H, Sellix MT, Rahman I 2015. Circadian molecular clock in lung pathophysiology. American Journal of Physiology-Lung Cellular and Molecular Physiology, 309: L1056-L1075.
Szymczak I, Wieczfinska J, Pawliczak R 2016. Molecular background of miRNA role in asthma and COPD: an updated insight. BioMed research international, 2016: 7802521
Taguchi A, Yanagisawa K, Tanaka M, Cao K, Matsuyama Y et al. 2008. Identification of hypoxia-inducible factor-1α as a novel target for miR-17-92 microRNA cluster. Cancer research, 68: 5540-5545.
Uchida T, Rossignol F, Matthay MA, Mounier R, Couette S et al. 2004. Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1α and HIF-2α expression in lung epithelial cells IMPLICATION OF NATURAL ANTISENSE HIF-1α. Journal of Biological Chemistry, 279: 14871-14878.
Wang R, Xu J, Liu H, Zhao Z 2017. Peripheral leukocyte micrornas as novel biomarkers for COPD. International journal of chronic obstructive pulmonary disease, 12: 1101–1112.
Xia G, Bao L, Gao W, Liu S, Ji K, Li J 2015. Differentially expressed miRNA in inflammatory mucosa of chronic rhinosinusitis. Journal of nanoscience and nanotechnology, 15: 2132-2139.
Xie L, Wu M, Lin H, Liu C, Yang H et al. 2014. An increased ratio of serum miR-21 to miR-181a levels is associated with the early pathogenic process of chronic obstructive pulmonary disease in asymptomatic heavy smokers. Molecular BioSystems, 10: 1072-1081.
Zhou Y, Schneider DJ, Blackburn MR 2009. Adenosine signaling and the regulation of chronic lung disease. Pharmacology & therapeutics, 123: 105-116.
Zong D, Ouyang R, Li J, Chen Y, Chen P 2016. Notch signaling in lung diseases: focus on Notch1 and Notch3. Therapeutic Advances in Respiratory Disease, 10: 468-484.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.