|
| miRNA | Cell/tissue/body fluid (models) | miRNA regulation; validation method | Predicted target gene/possible effect | References |
|
| Asthma | | | | |
| let-7 family (miR-98, let-7d, -7f, -7g, and -7i) | A549 cells and primary cultured T-cells (C) | Down; qRT-PCR, northern blotting | 3′-UTR of IL-13 | [81] |
| let-7 (a-e) and miR-200 (200b, and 141) families | Exosomes from BALF (H) | Differentially expressed; microarray, qRT-PCR | let-7 is associated with IL-13; miR-200 regulate EMT | [77] |
| miR-20b | Alveolar macrophages (M) | Down; qRT-PCR, transfection assay | ⊥miR-20b: ↑VEGF | [82] |
| miR-21 | Whole lung, macrophage, dendritic cells (M) | Up; microarray, qRT-PCR, ISH | IL-12p35 | [74, 83] |
| miR-106a | Mouse macrophage (M), Jurkat (T-cell), Raji (B-cell), THP-1 cells (C) | Up; qRT-PCR, northern blotting | IL-10; ⊥mmu-miR-106a: ↑IL-10, ↓asthma features | [84, 85] |
| miR-126 | Lower airway tissue (M) | Up; microarray, qRT-PCR | OBF.1 | [75, 86] |
| miR-133a | Bronchial smooth muscle cells and bronchial tissues of mice (C + M) | Down; qRT-PCR | ↓miR-133a: ↑RhoA | [76] |
| miR-145, -21, and let-7b | Lower airway tissue (M) | Up; qRT-PCR | ↓miR-145: ↓TH2 cytokine (IL-13, IL-5, IFN-) production | [87] |
| miR-146a, -146b, and -28-5p | Human circulating T cells (H + C) | Down; microarray, qRT-PCR | Involved in T-cell activation | [67] |
| miR-146a, -146b, and -181a | Spleen CD4+ T lymphocytes (M) | Up; qRT-PCR | Th2 inflammation; proinflammatory factors in asthma | [88] |
| miR-155 | Cell line and macrophages (C + M) | Up; microarray, qRT-PCR, transfection assay | ⊥miR-20b; ↑Glucocorticoids | [89] |
| miR-221 | Mice mast cell line (M + C), ASM cells cultured from bronchial biopsies (C + H) | Up; qRT-PCR, transfection assay | Augment cell proliferation and IL-6 production | [90, 91] |
| Chronic obstructive pulmonary disease (COPD) | | | | |
| let-7c and miR-125b | Induced sputum (H) | Down; qRT-PCR | ↓let-7c: ↑TNFR-II | [92] |
| miR-1 (muscle specific) | Muscle biopsy (H) | Down; qRT-PCR | IGF-1, HDAC4; ↓miR-1: ↓MRTF-SRF axis | [93] |
| miR-1, -499, -133, and -206 | Plasma (H) | Up in patient with stable COPD; qRT-PCR | miR-499 with markers of inflammation NF-B p50 | [94] |
| miR-7 | Serum (H) | Up; qRT-PCR | — | [95] |
| mir-15/107 family (miR-15b, -424, and -107), -223, and -1274a | Lung tissue (H) | Up; microarray, qRT-PCR, ISH, and transfection assay | ↑miR-15b: ↓SMAD7, SMAD7, decorin, and SMURF2 | [96] |
| miR-18a and -365 | Cell line, Lung tissue
(C + H) | Up; microarray, qRT-PCR, ISH, and transfection assay | — | [96, 97] |
| miR-20a, -28-3p, -34c-5p, and -100 | Serum (H) | Down; qRT-PCR | — | [95] |
| miR-26b, -29b, -101, -106b, -133b, -152, -483-5p, -532-5p, and -629 | Plasma (H) | Down; TaqMan low-density array screening; qRT-PCR | miR-106b level negatively correlates with disease progression | [78] |
| miR-101 and -144 | Human bronchial epithelial cell line (H + C), mice lung (C + M) | Up; qRT-PCR, luciferase assay, ISH | ↑miR-101: ↓CFTR: ↑COPD | [98] |
| miR-146a | Primary lung fibroblasts
(C + H) | Up; microarray, qRT-PCR | Degradation of COX-2 mRNA | [66] |
| miR-452 | Alveolar macrophages (H) | Down; microarray and qRT-PCR | ↑miR-452; ↓MMP12 | [99] |
| miR-923 and -937 | Lung tissue (H) | Down; microarray | Most downregulated in COPD | [96] |
| Cystic fibrosis (CF) | | | | |
| miR-14 and -494 | Several cell lines (C) | Up; qRT-PCR and luciferase assay | CFTR 3′-UTR | [100] |
| miR-101; -494 | HEK293 cell line (C) | Up; luciferase assays | ⊥CFTR | [101] |
| miR-101; -144 | Human bronchial epithelial cell line, mice lung (C + M) | Up; qRT-PCR, luciferase assay, and ISH | ↑miR-101: ↓CFTR: ↑COPD | [98] |
| miR-126 | Bronchial epithelial cell line (C) | Down; qRT-PCR and luciferase assay | ↓mir-126: ↑TOM1, TOLLIP | [102] |
| miR-138 | Primary human airway epithelial cells (H + C) | Up; qRT-PCR and luciferase assay | Regulate CFTR | [103] |
| miR-145, -223, and -494 | In vivo
bronchial brushings and cell lines (H + C) | Up; qRT-PCR and luciferase assay | Regulate CFTR | [104] |
| miR-145 and -494 | Nasal epithelial tissues (H) | Up; qRT-PCR | ↑miR-145: ↓SAMD3; ↑miR-494: ↓CFTR | [105] |
| miR-155 | Cell line, mouse (C + M) | Up; microarray and qRT-PCR | FGF7/KGF; ↑miR-155: ↓SHIP1, ↑IL-8 | [106–109] |
| miR-215 | Ex vivo CF lung epithelial cells (C) | Up; qRT-PCR | ↑IL-8 | [108] |
| miR-384, -494, and -1246 | Airway epithelial cells (C) | Down; qRT-PCR and luciferase assay | 3′- UTR of SLC12A2; ⊥CFTR | [100] |
| miR-509-3p and -494 | Primary human airway epithelial cells (H + C) | Up; qRT-PCR | Regulate CFTR expression | [110] |
| Idiopathic pulmonary fibrosis (IPF) | | | | |
| let-7d, miR-26, and miR-30 family | Lung biopsies and lung epithelial cells (M + C) | Down; microarray, qRT-PCR, and luciferase assay | ↓let-7d: ↑HMGA2 | [111] |
| miR-17~92 cluster | Lung biopsies (H) | Down; microarray and qRT-PCR | Metalloproteinases, collagen, and TGF | [112, 113] |
| miR-21 | Lung biopsies and serum (M + H) | Up; microarray, qRT-PCR, ISH, and luciferase assay | ↑TGF-, ⊥SMAD7; enhance EMT and IPF | [62–64, 114] |
| miR-29 | Lung tissues and pulmonary fibroblasts (M + C) | Down; microarray, qRT-PCR, ISH, and luciferase assay | Integrin, alpha 11; ADAMTS9; ADAM12, and nidogen-1 | [115–117] |
| miR-34a | Lung (M) | Up; microarray, qRT-PCR, ISH, and luciferase assay | — | [63] |
| miR-154, -134, -299–5p, -410, -382, -409–3p, -487b, -31, and -127 | Lung tissue + primary normal human lung fibroblast cells (H + C) | Up; microarray and qRT-PCR | SMAD3 to promoter of miR-154 | [118] |
| miR-200 family (a-c) | Lung (M) | Down | Inhibit TGF- 1 induced EMT of alveolar epithelial cells | [61] |
| Acute lung Injury (ALI) and inflammation | | | | |
| miR-127 | Mouse macrophage cell line (M + C) | Down; luciferase assay and microarray | IgG FcγRI (CD64); ↑miR-127: ↓cytokine from macrophages | [119] |
| Let-7; miR-21; -146; -155 | Lung (M) | Up; TaqMan low density arrays and qRT-PCR | Let-7 regulates IL-6; miR-146 –SMAD-4; miR-155 – SOCS-1 | [120] |
| miR-32*; -466-5p; -466-3p | Rat alveolar epithelial cell (R) | Up; microarray and qRT-PCR | — | [121] |
| miR-146a | Lung, macrophage cell line (R + C) | Up | ↑miR-146a: ⊥TNF-, IL-6, IL-1, IRAK-1, TRAF-6; | [122, 123] |
| miR-181b | Cell line (C) | Up; microarray and qRT-PCR | ↑miR-181b: ⊥Importin-α3; regulate NF-B signaling | [124] |
| Pulmonary arterial hypertension (PAH) | | | | |
| miR-17/92 cluster (miR-17-5p, -20a) | hPAECs (H + C) | Up; qRT-PCR; reporter gene assay | ↑miR-17/92; ↓BMPR2 protein; ↑STAT3 | [125] |
| miR-21 | hPASMC (H + C) | Up; qRT-PCR and western blotting | ↑miR-21: ↓(PDC4, SPRY2, PPAR, BMPR2); role in cell proliferation and migration | [126, 127] |
| miR-23b, -130a, and -191 | Blood buffy coat (H) | Up; qRT-PCR | miR-23b: ⊥BMPR1b; miR-130a:⊥BMPR1b, SMAD2 | [128] |
| miR-124 | hPASMC (H + C) | Down; qRT-PCR | NFATc1, CAMTA1 and PTBP1; inhibitor of NFAT signaling | [129] |
| miR-145 | hPASMC (H + C) and mouse (M) | Up; qRT-PCR | ↑miR-145; BMPR2 mutations; vessel remodeling | [130] |
| miR-204 | hPASMC (H + C), mouse (M), and rat lung (R) | Down; qRT-PCR | ↑STAT3, ↑SHP2;accounts for the proliferative and antiapoptotic phenotypes | [131] |
| miR-206 | Lung tissue + hPASMC
(H + C) and mouse (M) | Down; qRT-PCR | ↓Notch-3, HIF-1/Fhl-1 pathway; regulate proliferation | [132, 133] |
| miR-424 and 503 | hPAECs (H + C), mouse (M) and rat (R) lung endothelial cell (C) | Down; qRT-PCR | FGFR1, FGF2; antiproliferative effects | [134] |
| miR-451 and -1246 | Blood (H) | Down; qRT-PCR | miR-206: Titin; miR-1246: caveolin1, , and cadherin2 | [128] |
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