Table 2.
List of miRNAs involved in COPD pathogenesis and diagnosis.
| miRNA | Implication | Origin | Expression | Target Gene/Pathway | References |
|---|---|---|---|---|---|
| miR-452 | Control of airway inflammation and remodeling | Alveolar macrophages | Downregulated | MMP12 | (82) |
| miR-344b-1-3p | Modulator of the immune responses by CSE | Upregulated | TLR2 | (83) | |
| miR-637 | Development of pulmonary hypertension | Artery smooth muscle cells | Downregulated | CDK6 | (84) |
| miR-197 | Vascular remodeling and contraction | Downregulated | E2F1 | (85) | |
| mir-106a-363 and -106b cluster | COPD diagnosis and severity | BALF, plasma, leukocytes | Upregulated/downregulated | AKT1, PTEN, MYD88, IRAK4, IL6, TGF-βR | (86–88) |
| miR-146a | Inflammation and mucus secretion | BECs, fibroblasts, macrophages, plasma, lung tissue | Upregulated/downregulated | IRAK1/TRAF6, PGE2, COX2, PDE7A, IL-1R kinase-1 | (52, 89–95) |
| miR-195 | Cytokine production and inflammation | BECs, lung tissue | Upregulated | PHLPP2 | (96) |
| miR-132 | Direct correlation to FEV1/FVC% | BECs, monocytes, serum | Upregulated | SOCS5 | (97) |
| Profile of 9 miRNAs | Lung cancer prediction in COPD patients | Blood cells | Downregulated | SRCAP, DCTN5, ULK1, and SEMA7A | (98) |
| miR-183 (-5p) | Increases disease severity and pathogenesis | Blood, lungs, smooth muscle cells, leukocytes | Upregulated/downregulated | BKCaβ1, Autophagy, TLR, NSCLC, cardiomyopathy | (88, 99) |
| Profile of 5 miRNAs | Differentiating healthy, asthma and COPD | Breath exhaled condensate | Downregulated in asthma | IL-13, IL-5, GATA3, FcϵR1 β, IL-1 β, MMP-1, Mucin-1 | (100) |
| miR-29b | Regulation of cytokine expression | Bronchial epithelial cells | Downregulated | BRD4 | (101) |
| miR-10a-5p | Pathobiology of COPD and asthma | Upregulated | FOXO3 and PDE7A | (94) | |
| miR-132-212, -17-92, -192-194 clusters | COPD diagnosis against lung cancer | BALF | Downregulated | AKT1, ERBB2, KRAS, PTEN, MYD88 | (87) |
| miR-191 | Endothelial injury and inflammation | Circulating endothelial microparticles released by CSE | Upregulated | (102) | |
| miR-638 | Regulation of oxidative stress response | Emphysematous lung tissue | Upregulated | ADAM15, HDAC5, APBB1 | (103) |
| miR-126 | Endothelial injury and inflammation | Endothelial microparticles, ECs, UVECs | Upregulated/downregulated | ATM protein kinase | (102, 104) |
| miR-125a (-5p), 125b | Inflammation, severity and AECOPD | Endothelial microparticles, leukocytes, sputum, plasma | Upregulated | Autophagy, TLR, NSCLC, cardiomyopathy | (81, 88, 102, 105) |
| miR-503 | Correlate with pulmonary function (FEV1) | Lung fibroblasts | Downregulated | VEGF | (106) |
| miR-335-5p | Modification of fibroblast behavior and function | Downregulated | Rb1, CARF, and SGK3 | (107) | |
| miR-31-5p | Regulator of mucus hypersecretion | Lung tissue | Upregulated | ST3GAL2, PITPNM2, ARHGEF15 | (108) |
| miR-1274a, -424 | Emphysema and fibrosis. | Lung tissue and bronchial epithelial cells | Upregulated | IL-6, TEP1, CAT, TGFβ, and WNT pathway | (79) |
| miR-134-5p | Chronic mucus hypersecretion homeostasis | Downregulated | KRAS | (90) | |
| miR-150 | Suppression of CSE-induced inflammation | Downregulated | P53 | (109) | |
| miR-223 | Emphysema, fibrosis, immunity | Lung tissue, BECs | Upregulated | IL-6, TEP1, CAT, TGFβ, WNT, HDAC2 | (79, 110) |
| let-7 family (a,c,d) | Mucus, inflammation, malignancy | Lung tissue, BECs, BEC, sputum, serum | Upregulated/ downregulated | EDN1, IL-13, TGF- βR, TLR4, c-myc, TNFR-II | (78, 81, 90, 100, 102, 111, 112) |
| miR-21 | Lung function, inflammation, CRD differentiation | Lung tissue, BECs, exosomes, serum, plasma, BEC | Upregulated/downregulated | GF-β/Smad, PTEN, PI3K/HDAC2, Notch1, IL-13R, STAT3, IL-1 β | (95, 100, 113–119) |
| miR-101 | Mucus homeostasis and inflammation | Lung tissue, macrophages | Upregulated | MKP-1 | (120) |
| miR-218 (-5p) | Malignant transformation, lung function | Lung tissue, BECs, serum | Downregulated/ upregulated | BMI1, TNFR1 | (121–124) |
| miR-199a-5p | Negative correlation with pulmonary function | Lung tissue, PASMCs, Treg | Upregulated/downregulated | HIF-1α, SMAD3, TGF-β pathway | (125–127) |
| miR-146b | Regulating innate macrophage responses | Macrophages | Upregulated | STAT1 | (53) |
| profile of 8 miRNAs including miR-135b | Diagnosing AECOPD, inflammation | PBMCs, BECs | Upregulated | IL-1R1 and IL-1β | (128, 129) |
| miR-1273g-3p, -24-3p, -93-5p | Correlated with pulmonary function (FEV1) | Peripheral mononuclear cells | Downregulated | IL18, IL1B, TNF, NFKBIA, CCL3, and CCL4 | (130) |
| Profile of 5 miRNAs | Differentiation of COPD and asthma | Plasma | Different expression between COPD and asthma | Interferon-gamma inducible | (131) |
| Profile of 9 miRNAs | Differentiation of COPD | Plasma and airway epithelial cell EVs | 5 upregulated and 4 downregulated | Inflammation, extracellular matrix and remodeling | (132) |
| miR-206 | Apoptosis, atrophy, inflammation | pvASMCs, limb tissue, fibroblasts | Upregulated | Notch3, VEGF, HDAC3, HDAC4, IGF-1, SIRT-1, IRAK1 | (133–135) |
| miR-20a, -28-3p | COPD diagnosis | Serum | Downregulated | (136) | |
| Profile of 9 miRNAs | Environmental factors in COPD subjects | Differentially expressed | (137) | ||
| miR-1 | Atrophy | Serum / limb tissue | Downregulated / Upregulated | pAKT, HDAC3, HDAC4, IGF-1, SIRT-1 | (133, 138) |
| miR-7 | COPD diagnosis, inflammation | Serum, ASMCs | Upregulated | Epac1 | (136, 139) |
| miR-100 (-5p) | COPD severity | Serum, leukocytes | Downregulated/ upregulated | Autophagy, TLR, NSCLC, cardiomyopathy | (88, 136) |
| miR-34 (a, b, c, c-5p) | Lung function, apoptosis, emphysema | Serum, lung tissue, pmvECs, BECs, sputum | Downregulated/ upregulated | HIF-1α, Notch-1R, SIRT-1 and 6, SERPINE1 | (81, 125, 136, 140–142) |
| miR-181a, c | COPD development, inflammation, ROS | Serum, lung tissue, BECs | Downregulated | MMP, cell growth, apoptosis, NKs, CCN1 | (118, 143) |
| miR320a, b,d | CRD differentiation, lung function, inflammation | Serum, PBMCs, BECs | Upregulated | T‐cellR, FoxO, TGF‐β, MAPK, PI3K‐AKT, IL1B | (130, 144, 145) |
| miR-30a-3p | Correlate with pulmonary function (FEV1) | Sputum | Downregulated | (81) | |
| miR-145 | Differentiating CRDs, fibrosis and immunity | Sputum, serum, ASMCs, BECs, lung tissue, plasma | Upregulated/downregulated | SMAD3, KLF4 CFTR, KLF5 | (70, 111, 131, 146–148) |
| miR-338/(-3p) | Differentiation of asthma, COPD and ACO | Sputum, serum, plasma | Upregulated/ downregulated | RAB14, IGF2R | (70, 131) |
| miR-27a | Associated to muscle weakness and atrophy | Vastus lateralis from limb tissue | Upregulated | HDAC3, HDAC4, IGF-1 and SIRT-1 | (133) |