Araştırma Makalesi
BibTex RIS Kaynak Göster

Kronik obstrüktif akciğer hastalığında MIR16-1 ve MIR22'nin araştırılması

Yıl 2025, Cilt: 50 Sayı: 4, 1044 - 1052, 22.12.2025
https://doi.org/10.17826/cumj.1709716
https://izlik.org/JA36AE48YP

Öz

Amaç: Solunum yolu iltihabı ile karakterize kronik obstrüktif akciğer hastalığı (KOAH), yaşla birlikte sıklığı artan ve yüksek morbidite ve mortaliteye sahip bir akciğer hastalığıdır. MikroRNA (miRNA) olarak bilinen 19-25 nükleotid uzunluğundaki küçük kodlamayan RNA'lar, gen ekspresyonunun transkripsiyon sonrası seviyelerini kontrol eder. Birçok düzensiz miRNA'nın inflamasyon, kanser, hava yolu epitel farklılaşması ve akciğer gelişimi gibi çeşitli biyolojik yollarda yer aldığı gösterilmiştir. Bu nedenle, bu çalışmanın amacı, MIR16-1 ve MIR22’nin plazma ekspresyon seviyelerinin, KOAH tanısı ve takibi için bir kriter olarak kullanılıp kullanılamayacağını belirlemektir.
Gereç ve Yöntem: Bu çalışma toplam 58 erkek bireyi, 33 KOAH hastasını ve 25 sağlıklı kontrolü içermektedir. MIR16-1-3p ve MIR22-3p ekspresyon seviyelerini incelemek için gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) kullanıldı. Log2−delta delta CT (2-ΔΔCt) analizi, miRNA ekspresyon verilerini hesaplamak için kullanıldı.
Bulgular: MIR16-1-3p ve MIR22-3p ekspresyon seviyelerinde sağlıklı kontroller ve KOAH hastaları arasında anlamlı bir fark bulunmadı. KOAH hastaları stabil KOAH ve KOAH'ın akut alevlenmeleri olarak gruplandırıldığında, farklı gruplar arasında MIR16-1-3p ve MIR22-3p ekspresyon seviyelerinde bir değişiklik olmadı. Ek olarak, her iki miRNA'nın ekspresyon seviyeleri ile KOAH hastalarının klinik özellikleri arasında bir korelasyon bulunmadı.
Sonuç: Bu çalışmada, plazma MIR16-1-3p, MIR22-3p ekspresyon seviyeleri ile KOAH arasında bir ilişki olmadığı görüldü. Çalışma daha geniş bir örneklem büyüklüğüyle tekrarlanırsa, MIR16-1, MIR22 ve KOAH arasındaki bağlantının daha iyi anlaşılması mümkün olacaktır.

Kaynakça

  • Yang IA, Jenkins CR, Salvi SS. Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir Med. 2022;10:497-511.
  • Patel N. An update on COPD prevention, diagnosis, and management: The 2024 GOLD Report. Nurse Pract. 2024;49:29-36.
  • Bagdonas E, Raudoniute J, Bruzauskaite I, Aldonyte R. Novel aspects of pathogenesis and regeneration mechanisms in COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:995-1013.
  • Carrillo A, Ferrer M, Gonzalez-Diaz G, Lopez-Martinez A, Llamas N, Alcazar M et al. Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1279-85.
  • Uzun S, Djamin R, Hoogsteden H, Aerts J, van der Eerden M. Acute exacerbations of chronic obstructive pulmonary disease. In: Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung. Kayembe JM (ed). Chapter. 2013;4:77-98.
  • Agustí A, Melén E, DeMeo DL, Breyer-Kohansal R, Faner R. Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene-environment interactions across the lifespan. Lancet Respir Med. 2022;10:512-24.
  • Green CE, Clarke J, Bicknell R, Turner AM. Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer. Biomedicines. 2021;9:830.
  • Pelaia G, Vatrella A, Gallelli L, Renda T, Caputi M, Maselli R et al. Biological targets for therapeutic interventions in COPD: clinical potential. Int J Chron Obstruct Pulmon Dis. 2006;1:321-34.
  • Qian Y, Mao ZD, Shi YJ, Liu ZG, Cao Q, Zhang Q. Comprehensive analysis of miRNA-mRNA-lncRNA networks in non-smoking and smoking patients with chronic obstructive pulmonary disease. Cell Physiol Biochem. 2018;50:1154–63.
  • Corcoran MM, Hammarsund M, Zhu C, Lerner M, Kapanadze B, Wilson B, et al. DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse. Genes Chromosomes Cancer. 2004;40:285-97.
  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944-9..
  • Duan Y, Zhou M, Xiao J, Wu C, Zhou L, Zhou F et al. Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease. Int J Mol Med. 2016;38:1450-62.
  • Chen CH, Dixon RA, Ke LY, Willerson JT. Vascular progenitor cells in diabetes mellitus: roles of Wnt signaling and negatively charged low-density lipoprotein. Circ Res. 2009;9:1038-40.
  • Reuter S, Beckert H, Taube C. Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases. Lab Invest. 2015;2:177-85.
  • Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14:1902-10.
  • Jovicic A, Zaldivar Jolissaint JF, Moser R, Silva Santos Mde F, Luthi-Carter R. MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's disease-related mechanisms. PLoS One. 2013;8:e54222.
  • Gu W, Zhan H, Zhou XY, Yao L, Yan M, Chen A et al. MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin. FEBS Lett. 2017;591:513-26.
  • Lu W, You R, Yuan X, Yang T, Samuel EL, Marcano DC et al. The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema. Nat Immunol. 2015;16:1185-94.
  • Ming GF, Wu K, Hu K, Chen Y, Xiao J. NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway. Biochem Biophys Res Commun. 2016;478:1382-8.
  • Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513-8.
  • Alevizos I, Illei GG. MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol. 2010;6:391–8.
  • Agustí A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J. 2023;61:2300239.
  • Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.
  • Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;11:1231–43.
  • Banerjee A, Luettich K. MicroRNAs as potential biomarkers of smoking-related diseases. Biomark Med. 2012;6:671–84.
  • Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481:190-4.
  • Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, Zhou X et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci. 2012;8:118-23.
  • Wang G, Wang R, Strulovici-Barel Y, Salit J, Staudt MR, Ahmed J et al. Persistence of smoking-induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation. PLoS One. 2015;10:e0120824.
  • Willinger CM, Rong J, Tanriverdi K, Courchesne PL, Huan T, Wasserman GA et al. MicroRNA signature of cigarette smoking and evidence for a putative causal role of MicroRNAs in smoking-related inflammation and target organ damage. Circ Cardiovasc Genet. 2017;10:e001678.
  • Climent M, Viggiani G, Chen YW, Coulis G, Castaldi A. MicroRNA and ROS crosstalk in cardiac and pulmonary diseases. Int J Mol Sci. 2020;21:4370.
  • Mizuno S, Bogaard HJ, Gomez-Arroyo J, Alhussaini A, Kraskauskas D, Cool CD et al. MicroRNA-199a-5p is associated with hypoxia-inducible factor-1 expression in lungs from patients with COPD. Chest. 2012;142:663–72.
  • Liu L, Jiang H, Zhao J, Wen H. MiRNA-16 inhibited oral squamous carcinoma tumor growth in vitro and in vivo via suppressing Wnt/β-catenin signaling pathway. Onco Targets Ther. 2018;11:5111-9.
  • Kaur G, Begum R, Thota S, Batra S. A systematic review of smoking-related epigenetic alterations. Arch Toxicol. 2019;93:2715-40.
  • Donaldson A, Natanek SA, Lewis A, Man WD, Hopkinson NS, Polkey MI et al. Increased skeletal muscle-specific microRNA in the blood of patients with COPD. Thorax. 2013;68:1140-9.
  • Velasco-Torres Y, Ruiz V, Montaño M, Pérez-Padilla R, Falfán-Valencia R, Pérez-Ramos J et al. Participation of the miR-22-HDAC4-DLCO axis in patients with COPD by tobacco and biomass. Biomolecules. 2019;9:837.
  • O'Farrell HE, Bowman RV, Fong KM, Yang IA. Plasma extracellular vesicle miRNAs can identify lung cancer, current smoking status, and stable COPD. Int J Mol Sci. 2021;22:5803.
  • Matveev GA, Khromova NV, Zasypkin GG, Kononova YA, Vasilyeva EY, Babenko AY et al. Tissue and circulating MicroRNAs 378 and 142 as biomarkers of obesity and its treatment response. Int J Mol Sci. 2023;24:13426.
  • Portela A, Esteller M. Epigenetic modifcations and human disease. Nat Biotechnol. 2010;28:1057–68.

Investigation of MIR16-1 and MIR22 in chronic obstructive pulmonary disease

Yıl 2025, Cilt: 50 Sayı: 4, 1044 - 1052, 22.12.2025
https://doi.org/10.17826/cumj.1709716
https://izlik.org/JA36AE48YP

Öz

Purpose: Chronic obstructive pulmonary disease (COPD), characterized by respiratory tract inflammation, is a lung disease with increasing frequency with age and high morbidity and mortality. Small non-coding RNAs with a length of 19–25 nucleotides, known as microRNAs (miRNAs), control posttranscriptional levels of gene expression. Many dysregulated miRNAs have been demonstrated to be involved in various biological pathways like inflammation, cancer, airway epithelial differentiation, and lung development. Therefore, the aim of this study was to identify if MIR16-1 and MIR22 plasma expression levels might be utilized as a criterion for the diagnosis and monitoring of COPD.
Materials and Methods: This study contained a total of 58 male individuals, 33 COPD patients and 25 healthy controls. Real-time polymerase chain reaction (RT-PCR) was employed to examine the expression levels of MIR16-1-3p and MIR22-3p. Log2−delta delta CT (2-ΔΔCt) analysis was used to calculate miRNA expression data.
Results: No significant differences were discovered in the expression levels of MIR16-1-3p and MIR22-3p between healthy controls and COPD patients. When COPD patients were grouped as stable COPD and acute exacerbations of COPD, there was no change in the expression levels of MIR16-1-3p and MIR22-3p between different groups. Additionally, no correlation was found between the expression levels of either miRNA and the clinical features of COPD patients.
Conclusion: It was observed that there was no relationship between plasma MIR16-1-3p and MIR22-3p expression levels and COPD in this study. A deeper understanding of the connection between MIR16-1, MIR22, and COPD will be possible if the study is repeated with a wider sampling size.

Etik Beyan

Ethical approval was obtained from The Ethics Committee for Non-Interventional Scientific Research of Tokat Gaziosmanpasa University, Faculty of Medicine, with the registration number 25-MOBAEK-117 in its meeting dated 08.04.2025.

Destekleyen Kurum

None

Kaynakça

  • Yang IA, Jenkins CR, Salvi SS. Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir Med. 2022;10:497-511.
  • Patel N. An update on COPD prevention, diagnosis, and management: The 2024 GOLD Report. Nurse Pract. 2024;49:29-36.
  • Bagdonas E, Raudoniute J, Bruzauskaite I, Aldonyte R. Novel aspects of pathogenesis and regeneration mechanisms in COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:995-1013.
  • Carrillo A, Ferrer M, Gonzalez-Diaz G, Lopez-Martinez A, Llamas N, Alcazar M et al. Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:1279-85.
  • Uzun S, Djamin R, Hoogsteden H, Aerts J, van der Eerden M. Acute exacerbations of chronic obstructive pulmonary disease. In: Oncogenesis, Inflammatory and Parasitic Tropical Diseases of the Lung. Kayembe JM (ed). Chapter. 2013;4:77-98.
  • Agustí A, Melén E, DeMeo DL, Breyer-Kohansal R, Faner R. Pathogenesis of chronic obstructive pulmonary disease: understanding the contributions of gene-environment interactions across the lifespan. Lancet Respir Med. 2022;10:512-24.
  • Green CE, Clarke J, Bicknell R, Turner AM. Pulmonary MicroRNA Changes Alter Angiogenesis in Chronic Obstructive Pulmonary Disease and Lung Cancer. Biomedicines. 2021;9:830.
  • Pelaia G, Vatrella A, Gallelli L, Renda T, Caputi M, Maselli R et al. Biological targets for therapeutic interventions in COPD: clinical potential. Int J Chron Obstruct Pulmon Dis. 2006;1:321-34.
  • Qian Y, Mao ZD, Shi YJ, Liu ZG, Cao Q, Zhang Q. Comprehensive analysis of miRNA-mRNA-lncRNA networks in non-smoking and smoking patients with chronic obstructive pulmonary disease. Cell Physiol Biochem. 2018;50:1154–63.
  • Corcoran MM, Hammarsund M, Zhu C, Lerner M, Kapanadze B, Wilson B, et al. DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouse. Genes Chromosomes Cancer. 2004;40:285-97.
  • Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102(39):13944-9..
  • Duan Y, Zhou M, Xiao J, Wu C, Zhou L, Zhou F et al. Prediction of key genes and miRNAs responsible for loss of muscle force in patients during an acute exacerbation of chronic obstructive pulmonary disease. Int J Mol Med. 2016;38:1450-62.
  • Chen CH, Dixon RA, Ke LY, Willerson JT. Vascular progenitor cells in diabetes mellitus: roles of Wnt signaling and negatively charged low-density lipoprotein. Circ Res. 2009;9:1038-40.
  • Reuter S, Beckert H, Taube C. Take the Wnt out of the inflammatory sails: modulatory effects of Wnt in airway diseases. Lab Invest. 2015;2:177-85.
  • Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14:1902-10.
  • Jovicic A, Zaldivar Jolissaint JF, Moser R, Silva Santos Mde F, Luthi-Carter R. MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's disease-related mechanisms. PLoS One. 2013;8:e54222.
  • Gu W, Zhan H, Zhou XY, Yao L, Yan M, Chen A et al. MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin. FEBS Lett. 2017;591:513-26.
  • Lu W, You R, Yuan X, Yang T, Samuel EL, Marcano DC et al. The microRNA miR-22 inhibits the histone deacetylase HDAC4 to promote T(H)17 cell-dependent emphysema. Nat Immunol. 2015;16:1185-94.
  • Ming GF, Wu K, Hu K, Chen Y, Xiao J. NAMPT regulates senescence, proliferation, and migration of endothelial progenitor cells through the SIRT1 AS lncRNA/miR-22/SIRT1 pathway. Biochem Biophys Res Commun. 2016;478:1382-8.
  • Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105:10513-8.
  • Alevizos I, Illei GG. MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol. 2010;6:391–8.
  • Agustí A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P et al. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J. 2023;61:2300239.
  • Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3:1101–8.
  • Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;11:1231–43.
  • Banerjee A, Luettich K. MicroRNAs as potential biomarkers of smoking-related diseases. Biomark Med. 2012;6:671–84.
  • Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481:190-4.
  • Zhou Q, Li M, Wang X, Li Q, Wang T, Zhu Q, Zhou X et al. Immune-related microRNAs are abundant in breast milk exosomes. Int J Biol Sci. 2012;8:118-23.
  • Wang G, Wang R, Strulovici-Barel Y, Salit J, Staudt MR, Ahmed J et al. Persistence of smoking-induced dysregulation of miRNA expression in the small airway epithelium despite smoking cessation. PLoS One. 2015;10:e0120824.
  • Willinger CM, Rong J, Tanriverdi K, Courchesne PL, Huan T, Wasserman GA et al. MicroRNA signature of cigarette smoking and evidence for a putative causal role of MicroRNAs in smoking-related inflammation and target organ damage. Circ Cardiovasc Genet. 2017;10:e001678.
  • Climent M, Viggiani G, Chen YW, Coulis G, Castaldi A. MicroRNA and ROS crosstalk in cardiac and pulmonary diseases. Int J Mol Sci. 2020;21:4370.
  • Mizuno S, Bogaard HJ, Gomez-Arroyo J, Alhussaini A, Kraskauskas D, Cool CD et al. MicroRNA-199a-5p is associated with hypoxia-inducible factor-1 expression in lungs from patients with COPD. Chest. 2012;142:663–72.
  • Liu L, Jiang H, Zhao J, Wen H. MiRNA-16 inhibited oral squamous carcinoma tumor growth in vitro and in vivo via suppressing Wnt/β-catenin signaling pathway. Onco Targets Ther. 2018;11:5111-9.
  • Kaur G, Begum R, Thota S, Batra S. A systematic review of smoking-related epigenetic alterations. Arch Toxicol. 2019;93:2715-40.
  • Donaldson A, Natanek SA, Lewis A, Man WD, Hopkinson NS, Polkey MI et al. Increased skeletal muscle-specific microRNA in the blood of patients with COPD. Thorax. 2013;68:1140-9.
  • Velasco-Torres Y, Ruiz V, Montaño M, Pérez-Padilla R, Falfán-Valencia R, Pérez-Ramos J et al. Participation of the miR-22-HDAC4-DLCO axis in patients with COPD by tobacco and biomass. Biomolecules. 2019;9:837.
  • O'Farrell HE, Bowman RV, Fong KM, Yang IA. Plasma extracellular vesicle miRNAs can identify lung cancer, current smoking status, and stable COPD. Int J Mol Sci. 2021;22:5803.
  • Matveev GA, Khromova NV, Zasypkin GG, Kononova YA, Vasilyeva EY, Babenko AY et al. Tissue and circulating MicroRNAs 378 and 142 as biomarkers of obesity and its treatment response. Int J Mol Sci. 2023;24:13426.
  • Portela A, Esteller M. Epigenetic modifcations and human disease. Nat Biotechnol. 2010;28:1057–68.
Toplam 38 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Göğüs Hastalıkları, Tıbbi Biyokimya - Nükleik Asitler
Bölüm Araştırma Makalesi
Yazarlar

Nevin Karakuş 0000-0002-1916-7471

Sümeyye Yıldırım 0009-0008-5402-3140

Gönderilme Tarihi 30 Mayıs 2025
Kabul Tarihi 24 Kasım 2025
Yayımlanma Tarihi 22 Aralık 2025
DOI https://doi.org/10.17826/cumj.1709716
IZ https://izlik.org/JA36AE48YP
Yayımlandığı Sayı Yıl 2025 Cilt: 50 Sayı: 4

Kaynak Göster

MLA Karakuş, Nevin, ve Sümeyye Yıldırım. “Investigation of MIR16-1 and MIR22 in chronic obstructive pulmonary disease”. Cukurova Medical Journal, c. 50, sy 4, Aralık 2025, ss. 1044-52, doi:10.17826/cumj.1709716.