TABLE 2.
Overlapping microRNAs (miRNAs) in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF)
| miRNAs | Specimen | Method | Target mRNA | Design | Subjects n | [Ref.] |
| 29a-3p | SSc and normal dermal fibroblasts | miR-29a-3p mimic/antimir | Bcl-2 Bax | Case–control | dcSSc=10, controls=10 | [18] |
| 29a-3p, 29b-3p, 29c-3p, pre-mir-29a, pre-mir-29b | Dermal fibroblasts | qPCR, pre-mir29a/b mimic | N/A | Cross-sectional | Controls=9 | [17] |
| 29a-3p, 29b-3p, 29c-3p, pre-mir-29a, pre-mir-29b, pre-mir-29c | SSc and normal skin biopsy; dermal fibroblasts | qPCR, pre-miR29a/b/c mimic/antimir | COL1A1, COL3A1 | Case–control | SSc=12, controls=11 | [15] |
| 29c-3p, pre-mir-29c | IPF and normal lung biopsy; primary mesenchymal cells and controls; pulmonary fibroblasts | qPCR, miR-29c-3p overexpression/knockdown lentiviral transfection | N/A | Case–control | IPF=11, controls=10 | [22] |
| 29c-3p | IPF and normal lung biopsy; pulmonary fibroblasts; decellularised primary human lung; ECM | qPCR, miR-29c-3p lentiviral transfection | COL6A2, LAMA2, COL4A2, COL1A2, LAMC1, COL4A1, COL1A1, COL5A1, NID1, MFAP2 | Case–control | IPF=5, controls=5 | [23] |
| 21-5p | SSc and normal skin biopsy; dermal fibroblasts | qPCR, in situ hybridisation, miR-21-5p mimic/antimir | FN1, ACTA2, COL1A1, COL1A2 | Case–control | dcSSc=4, lcSSc=2, controls=4 | [28] |
| 9-5p, 10a-5p, 15a-5p, 21-5p, 31-5p, 125a-5p, 125b-5p, 137-3p, 181a-5p, 203a-3p, 218-5p, 381-3p, 410, let-7a-5p, let-7b-5p, let-7c | Serum | Array, initial qPCR for miR-146a-5p, 155-5p, let-7a-5p, 181a-5p, 454-5p, let-7b-5p, 28-3p and miR-885-5p; confirmatory qPCR for miR-21-5p, 199a-5p, 200c-3p, 31-5p, let-7a-5p and let-7d-5p | N/A | Case–control | Rapidly progressive=12, slowly progressive IPF=12, controls for profiling=12; rapidly progressive IPF=20, slowly progressive IPF =24, controls=20 for qPCR confirmation | [24] |
| 21-5p, 155-5p | Serum | qPCR | N/A | Case–control | IPF=65, controls=65 | [30] |
| 21-5p | IPF and normal lung biopsy; MRC-5 and IMR-90, HEK-293 cells | Northern blotting, in situ hybridisation, miR-21-5p mimic/antimir | N/A | Case–control | IPF=8, controls=8 | [31] |
| 21-5p | IPF and normal lung biopsy; human alveolar type 2 cells | qPCR, in situ hybridisation | N/A | Case–control | IPF=3, controls=3 | [32] |
| 21-5p, 29a-3p, 92a-3p, 101-3p, 106a-5p, 142-3p, 155-5p, 181b-5p-5p, 184-3p, 223-3p, 342-3p, 409-3p, let-7c | Serum | qPCR | N/A | Cross-sectional | dcSSc=32, lcSSc=63 | [21] |
| 17-5p, 20a-5p, 29b-3p, 92a-3p, 106a-5p, 142-3p, 145-5p, 146b-5p, 181b-5p-5p, 221-3p, 223-3p, 342-3p | Serum | qPCR | N/A | Case–control | dcSSc=41, lcSSc=79, SLE=29, controls=40 | [20] |
| 26a-5p, 30a-5p, 30b-5p, 30d-5p, 92a-3p, 101-3p, 125a-5p, 126-3p, 184-3p, 203a-3p, 218-5p, 222-3p, 375-3p, let-7d-5p, let-7g-5p | IPF and normal lung biopsy; pulmonary fibroblasts | qPCR, miR-30a-5p, 30d-5p, 92a-3p mimic/antimir | WISP1 | Case–control | IPF=8, controls=7 | [37] |
| 92a-3p | SSc and normal skin biopsy; dermal fibroblasts; serum | qPCR, miR-92a-3p mimic | N/A | Case–control | dcSSc=23, lcSSc=38, SSD=12, DM=7, SLE=7, controls=18 | [34] |
| 17∼92 cluster (17-5p, 18a-5p, 19a-3p, 19b-3p, 20a-5p, 92a-3p) | IPF and COPD lung biopsy; normal and IPF pulmonary fibroblasts | qPCR, in situ hybridisation, miR-17∼92 mimic/antimir | N/A | Case–control | >80% FVC IPF+COPD=7, 50–80% FVC IPF+COPD=8, <50% FVC IPF+COPD=9, controls=10 | [38] |
| 26a-5p, 27b-3p, 30a-5p, 30d-5p, 92a-3p, 125a-5p, 125b-5p, 140-5p, 145-5p, 197-3p, 214-3p, 377-3p, 381-3p, 486-5p, let-7g-5p | Skin biopsy | Array, qPCR let-7g-5p, 206-3p, 125b-5p | N/A (identified by computational prediction algorithms) | Case–control | SSc=3, controls=3 | [36] |
| 21-5p, 29b-3p, 31-5p, 145-5p, 146a-5p, 503-5p | SSc and normal skin biopsy; dermal fibroblasts | Array, qPCR for miR-21, 31, 503, 146, 145, 29b | SMAD7, SMAD3 COL1A1 | Case–control | dcSSc=5, lcSSc=2, controls=7 | [16] |
| 30a-3p | SSc and normal skin; rheumatoid arthritis and normal synovial biopsy; dermal fibroblasts, fibroblasts-like synoviocytes | qPCR, miR-30a-3p mimic/antimir | BAFF | Case–control | FLS: RA=5, controls=5; DF: SSc=4, controls=3 |
[50] |
| 9-5p, 10a-5p, 15a-5p, 17-5p, 18a-5p, 20a-5p, 21-5p, 22-3p, 26a-5p, 92a-3p, 93-5p, 96-5p, 100-5p, 101-3p, 103a-3p, 106b-5p, 125a-5p, 126-3p, 130a-3p, 132-3p, 133b-3p, 134, 137-3p, 141-3p, 142-3p, 142-5p, 146a-5p, 155-5p, 181a-5p, 182-5p, 205-5p, 210, 214-3p, 222-3p, 223-3p, 301a-3p, 302c-3p, 345-5p, 370, 375-3p, 424-5p, 520g, let-7a-5p, let-7b, let-7c, let-7d-5p, let-7g-5p | Serum; dermal fibroblasts; skin tissues | Array, qPCR for let-7a-5p, in situ hybridisation, let-7a mimic/antimir | N/A | Case–control | Serum: dcSSc=20, lcSSc=19, LSc=39, SLE=8, DM=8, controls=17; skin tissues: SSc=7, LSc=7, keloid=5, controls=7 |
[43] |
| 19a-5p, 26a-5p, 30b-5p, 106b-5p, 181a-5p, 181b-5p, 203a-3p, 205-5p, 302c-3p, 409-3p, 410 let-7a-5p, let-7b-5p, let-7c, let-7d-5p | SSc and normal skin biopsy; dermal fibroblasts; serum | qPCR, miR-30b-5p mimic | PDGFR-β, COL1A2, ACTA2 | Case–control | dcSSc=18, lcSSc=32, controls=24 | [45] |
| 10a-5p, 15a-5p, 17-5p, 18a-5p, 20a-5p, 21-5p, 93-5p, 96-5p, 101-3p, 103a-3p, 106b-5p, 130a-3p, 132-3p, 133b-3p, 134, 137-3p, 141-3p, 142-5p, 142-3p, 155-5p, 182-5p, 210, 301a-3p, 370, 424-5p, 520g, let-7a-5p, let-7b-5p, let-7c, let-7d-5p, let-7g-5p | SSc and normal skin biopsy; dermal fibroblasts | Array, qPCR for miR-150, in situ hybridisation, miR-150 mimic | N/A | Case–control | Serum: dcSSc=20, lcSSc=20, DM=5, SLE=5, controls=20; skin tissues: dcSSc=5, controls=5 |
[46] |
| 1-3p, 9-5p, 10a-5p, 15a-5p, 17-5p, 18a-5p, 20a-5p, 21-5p, 22-3p, 26a-5p, 92a-3p, 93-5p, 96-5p, 100-5p, 101-3p, 103a-3p, 106b-5p, 125a-5p, 126-3p, 128-3p, 130a-3p, 132-3p, 133b-3p, 134, 137-3p, 142-5p, 142-3p, 155-5p, 181a-5p, 182-5p, 205-5p, 210, 214-3p, 218-5p, 222-3p, 223-3p, 301a-3p, 302c-3p, 370, 375-3p, 424-5p, 520g, let-7a-5p, let-7b-5p, let-7c, let-7d-5p, let-7g-5p | SSc and normal skin biopsy; dermal fibroblasts | Array, qPCR for miR-196a, miR-196a mimic/antimir | N/A | Case–control | Serum: dcSSc=20, lcSSc=20, controls=25; skin tissues: SSc=5, TGF-β-stimulated=5, controls=5 |
[49] |
| 1-3p | SSc and normal dermal fibroblasts | Array | N/A | Case–control | Skin tissues: dcSSc=6, controls=8 | [54] |
| 142-3p | Serum | qPCR | N/A | Case–control | dcSSc=23, lcSSc=38, SSD=12, controls=20, SLE=8, DM=8 | [51] |
| 9-5p | IPF and normal lung biopsy; human fetal lung fibroblasts; human mesothelial cells | Array, qPCR for miR-9-5p, in situ hybridisation, pre-miR-9-5p mimic/antimir | TGFBR2, NOX4, ACTA2, COL1A1, FN1 | Case–control | IPF=7, controls=3 | [55] |
| 31-5p, 424-5p | TGF-β1 stimulated and normal human lung epithelial cells (A549) | Array, miR-424-5p, 1224-5p and 23b-3p overexpression/knockdown lentiviral transfection | N/A | Case–control | Cells | [57] |
| 96-5p | IPF and normal lung biopsy; pulmonary fibroblasts | qPCR, in situ hybridisation, miR-96-5p mimic/antimir | FoxO3a, p27, p21, BIM | Case–control | IPF=8, controls=8 | [53] |
| 210 | IPF and normal lung biopsy; lung mesenchymal cells |
qPCR, in situ hybridisation, miR-210 overexpression/knockdown lentiviral transfection | N/A | Case–control | IPF=7, controls=6 | [48] |
| 26a-5p | Human lung epithelial cells (A549) | Array (downloaded from Gene Expression Omnibus database), miR-26a-5p mimic/antimir | Human genes annotated in the biological process of “EMT” were downloaded from the Gene Ontology database (GO:0001837) | Case–control | Cells | [41] |
| 26a-5p, 30a-5p, 30b-5p, 133b-3p | IPF and normal lung biopsy; human fetal lung fibroblasts | Array, miR-26a-5p mimic | COL1A1, COL3A1 | Case–control | IPF=8, controls=10 cells | [40] |
| let-7d-5p | Human fetal lung fibroblasts, human lung fibroblasts, human fetal foreskin fibroblasts |
let-7d-5p overexpression lentiviral transfection | PAI-1, HMGA2, ACTA2, CDH2, ID1, ID2, SLUG, FSP-1, FN1, KRT19 | Case–control | Cells | [47] |
| 140-5p | Human type II alveolar epithelial cells (A549) | qPCR, miR-140-5p mimic/antimir | Case–control | IPF=5, controls=5 cells | [56] | |
| 1-3p, 10a-5p, 17-5p, 27b-3p, 30a-3p, 30a-5p, 30b-3p, 30d-5p, 126-3p, 133b-3p, 181a-5p, 184-3p-3p, 203a-3p, 210, 222-3p, 370, 375-3p, 377-3p, 381-3p, 409-3p, 410, 520g, let-7d-5p | IPF and normal lung biopsy; IPF, TGF-β-stimulated and normal human lung fibroblasts | Array, miR-154-5p mimic/antimir | MEG3, DKK2, DIXDC1, PPP2CA, FZD 4/5/6, LRP, KREMEN1, β-CATENIN, WISP1 | Case–control | IPF=13, controls=12; IPF=32, controls=28 for qPCR confirmation | [44] |
| 15a-5p, 17-5p, 18a-5p, 19a-5p, 20a-5p, 21-5p, 22-3p, 27b-3p, 29a-3p, 29b-3p, 29c-3p, 30a-5p, 30b-5p, 92a-3p, 93-5p, 96-5p, 100-5p, 101-3p, 103a-3p, 106b, 125a-5p, 126-3p, 128, 130a, 140-5p, 141, 142-3p, 142-5p, 155, 181b-5p, 210, 222-3p, 223-3p, 302c-3p, 424-5p, let-7c, let-7d-5p | IPF and normal lung biopsy, IPF and normal lung fibroblasts | Array | N/A | Case–control | Rapidly progressive IPF=9, slowly progressive IPF=6, controls=10 | [29] |
| 26a-5p, 30a-3p, 30b-5p, 30d-5p, 92a-3p, 125a-5p, 126-3p, 132-3p, 134, 155-5p, 182-5p, 184-3p, 197-3p, 203a-3p, 205-5p, 214-3p, 409-3p, let-7d-5p | IPF and normal lung tissues, A549 cells | Array, qPCR for 26a-5p, 30a-3p, 30b-5p, 30d-5p, 92a-3p, let-7d-5p mimic/inhibitor | HMGA2, CDH2, VIM, ACTA2 | Case–control | IPF=10, controls=10 cells | [39] |
| 130a-3p, 142-5p | BAL fluid samples; IPF and normal macrophages | qPCR | N/A | Case–control | IPF=9, control=7 | [52] |
| 29a-3p | SSc and normal skin biopsy; dermal fibroblasts | qPCR, mir-29a mimic | COL1A1, TIMP1, TAB1 | Case–control | SSc=4–6, controls=4–6 | [19] |
| 130b-3p | SSc and normal skin biopsy; dermal fibroblasts | qPCR, miR-130b-3p mimic/antimir | COL1A1, COL1A2, FN1, ASMA | Case-control | SSc=14, controls=14 | [58] |
| 130b-3p | IPF and normal lung biopsy; human primary type II alveolar epithelial and lung fibroblasts | qPCR, miR-130b-3p mimic/antimir | IGF1 | Case–control | IPF=4, controls=3 | [59] |
| 26a-5p, let-7d-5p | Human alveolar basal epithelial cells | qPCR, miR-26a-5p mimic/antimir | LIN28B | Case–control | IPF=106, controls=50 (microarray data set of GSE32538) | [42] |
| 29b-3p | IPF lung biopsy | qPCR, miR-29b-3p mimic | COL1A1, COL3A1 | Case–control | IPF=16 | [25] |
The table describes all the manuscripts that reported overlapping miRNAs between SSc and IPF. The manuscripts have been categorised according to the significance, specimen analysed, miRNAs detection method employed and, where described, the mRNA target. Moreover, the design of the study and the number of subjects involved in each study, together with the reference, are reported. Bcl-2: B-cell lymphoma 2; BAX: bcl-2-like protein 4; dcSSc: diffuse cutaneous SSc; COL1A1, COL1A2, etc.: collagen, type I, alpha 1, collagen, type I, alpha 2, etc.; ECM: extracellular matrix; LAMA2: laminin, alpha 2; LAMC1: laminin, gamma 1; NID1: nidogen 1; MFAP2: microfibrillar-associated protein 2; FN1: fibronectin 1; ACTA: alpha smooth muscle actin; lcSSc: limited cutaneous SSc; MRC-5: Medical Research Council cell strain 5; HEK-293: human embryonic kidney cells 293; SLE: systemic lupus erythematosus; WISP1: WNT1-inducible-signalling pathway protein 1; SSD: scleroderma spectrum disorders; DM: dermatomyositis; COPD: chronic obstructive pulmonary disease; N/A: not available; FVC: forced vital capacity; SMAD: small mother against decapentaplegic protein; BAFF: B-cell activating factor; FLS: fibroblast-like synoviocytes; RA: rheumatoid arthritis; DF: dermal fibroblasts; LSc: localised scleroderma; PDGFR-β: platelet-derived growth factor receptor β; TGF-β: transforming growth factor-β; NOX4: NADPH oxidase 4; FoxO3a: Forkhead box O3; BIM: Bcl-2-like protein 11; EMT: epithelial–mesenchymal transition; PAI-1: plasminogen activator inhibitor-1; HMGA2: high-mobility group AT-hook 2; CDH2: cadherin-2; ID1–ID2: DNA-binding protein inhibitor 1–2; SLUG: protein snail homolog 2; FSP-1: fibroblast-specific protein 1; KRT19: keratin 19; MEG3: maternally expressed 3; DKK2: Dickkopf WNT signaling pathway inhibitor 2; DIXDC1: DIX domain containing 1; PP2CA: protein phosphatase 2CA; FZD4-5-6: frizzled-4 frizzled-5 frizzled-6; LRP: lipoprotein receptor-related protein; KREMEN: Kringle-Containing Protein Marking the Eye and the Nose; VIM: vimentin; BAL: bronchoalveolar lavage; TIMP: tissue inhibitor of metalloproteinase 1; TAB1: TGF-β activated kinase 1/MAP3K7 binding protein 1; ASMA: a smooth muscle actin; IGF: insulin-like growth factor.