Overlapping microRNAs (miRNAs) in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF)

miRNAsSpecimenMethodTarget mRNADesignSubjects n[Ref.]
29a-3pSSc and normal dermal fibroblastsmiR-29a-3p mimic/antimirBcl-2 BaxCase–controldcSSc=10, controls=10[18]
29a-3p, 29b-3p, 29c-3p, pre-mir-29a, pre-mir-29bDermal fibroblastsqPCR, pre-mir29a/b mimicN/ACross-sectionalControls=9[17]
29a-3p, 29b-3p, 29c-3p, pre-mir-29a, pre-mir-29b, pre-mir-29cSSc and normal skin biopsy; dermal fibroblastsqPCR, pre-miR29a/b/c mimic/antimirCOL1A1, COL3A1Case–controlSSc=12, controls=11[15]
29c-3p, pre-mir-29cIPF and normal lung biopsy; primary mesenchymal cells and controls; pulmonary fibroblastsqPCR, miR-29c-3p overexpression/knockdown lentiviral transfectionN/ACase–controlIPF=11, controls=10[22]
29c-3pIPF and normal lung biopsy; pulmonary fibroblasts; decellularised primary human lung; ECMqPCR, miR-29c-3p lentiviral transfectionCOL6A2, LAMA2, COL4A2, COL1A2, LAMC1, COL4A1, COL1A1, COL5A1, NID1, MFAP2Case–controlIPF=5, controls=5[23]
21-5pSSc and normal skin biopsy; dermal fibroblastsqPCR, in situ hybridisation, miR-21-5p mimic/antimirFN1, ACTA2, COL1A1, COL1A2Case–controldcSSc=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-7cSerumArray, 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-5pN/ACase–controlRapidly 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, 155-5pSerumqPCRN/ACase–controlIPF=65, controls=65[30]
21-5pIPF and normal lung biopsy; MRC-5 and IMR-90, HEK-293 cellsNorthern blotting, in situ hybridisation, miR-21-5p mimic/antimirN/ACase–controlIPF=8, controls=8[31]
21-5pIPF and normal lung biopsy; human alveolar type 2 cellsqPCR, in situ hybridisationN/ACase–controlIPF=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-7cSerumqPCRN/ACross-sectionaldcSSc=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, 342-3pSerumqPCRN/ACase–controldcSSc=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-5pIPF and normal lung biopsy; pulmonary fibroblastsqPCR, miR-30a-5p, 30d-5p, 92a-3p mimic/antimirWISP1Case–controlIPF=8, controls=7[37]
92a-3pSSc and normal skin biopsy; dermal fibroblasts; serumqPCR, miR-92a-3p mimicN/ACase–controldcSSc=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 fibroblastsqPCR, in situ hybridisation, miR-17∼92 mimic/antimirN/ACase–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-5pSkin biopsyArray, qPCR let-7g-5p, 206-3p, 125b-5pN/A (identified by computational prediction algorithms)Case–controlSSc=3, controls=3[36]
21-5p, 29b-3p, 31-5p, 145-5p, 146a-5p, 503-5pSSc and normal skin biopsy; dermal fibroblastsArray, qPCR for miR-21, 31, 503, 146, 145, 29bSMAD7, SMAD3 COL1A1Case–controldcSSc=5, lcSSc=2, controls=7[16]
30a-3pSSc and normal skin; rheumatoid arthritis and normal synovial biopsy; dermal fibroblasts, fibroblasts-like synoviocytesqPCR, miR-30a-3p mimic/antimirBAFFCase–controlFLS: RA=5, controls=5;
DF: SSc=4, controls=3
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-5pSerum; dermal fibroblasts; skin tissuesArray, qPCR for let-7a-5p, in situ hybridisation, let-7a mimic/antimirN/ACase–controlSerum: dcSSc=20, lcSSc=19, LSc=39, SLE=8, DM=8, controls=17;
skin tissues: SSc=7, LSc=7, keloid=5, controls=7
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-5pSSc and normal skin biopsy; dermal fibroblasts; serumqPCR, miR-30b-5p mimicPDGFR-β, COL1A2, ACTA2Case–controldcSSc=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-5pSSc and normal skin biopsy; dermal fibroblastsArray, qPCR for miR-150, in situ hybridisation, miR-150 mimicN/ACase–controlSerum: dcSSc=20, lcSSc=20, DM=5, SLE=5, controls=20;
skin tissues: dcSSc=5, controls=5
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-5pSSc and normal skin biopsy; dermal fibroblastsArray, qPCR for miR-196a, miR-196a mimic/antimirN/ACase–controlSerum: dcSSc=20, lcSSc=20, controls=25;
skin tissues: SSc=5, TGF-β-stimulated=5, controls=5
1-3pSSc and normal dermal fibroblastsArrayN/ACase–controlSkin tissues: dcSSc=6, controls=8[54]
142-3pSerumqPCRN/ACase–controldcSSc=23, lcSSc=38, SSD=12, controls=20, SLE=8, DM=8[51]
9-5pIPF and normal lung biopsy; human fetal lung fibroblasts; human mesothelial cellsArray, qPCR for miR-9-5p, in situ hybridisation, pre-miR-9-5p mimic/antimirTGFBR2, NOX4, ACTA2, COL1A1, FN1Case–controlIPF=7, controls=3[55]
31-5p, 424-5pTGF-β1 stimulated and normal human lung epithelial cells (A549)Array, miR-424-5p, 1224-5p and 23b-3p overexpression/knockdown lentiviral transfectionN/ACase–controlCells[57]
96-5pIPF and normal lung biopsy; pulmonary fibroblastsqPCR, in situ hybridisation, miR-96-5p mimic/antimirFoxO3a, p27, p21, BIMCase–controlIPF=8, controls=8[53]
210IPF and normal lung biopsy; lung
mesenchymal cells
qPCR, in situ hybridisation, miR-210 overexpression/knockdown lentiviral transfectionN/ACase–controlIPF=7, controls=6[48]
26a-5pHuman lung epithelial cells (A549)Array (downloaded from Gene Expression Omnibus database), miR-26a-5p mimic/antimirHuman genes annotated in the biological process of “EMT” were downloaded from the Gene Ontology database (GO:0001837)Case–controlCells[41]
26a-5p, 30a-5p, 30b-5p, 133b-3pIPF and normal lung biopsy; human fetal lung fibroblastsArray, miR-26a-5p mimicCOL1A1, COL3A1Case–controlIPF=8, controls=10 cells[40]
let-7d-5pHuman fetal lung fibroblasts, human lung fibroblasts, human fetal
foreskin fibroblasts
let-7d-5p overexpression lentiviral transfectionPAI-1, HMGA2, ACTA2, CDH2, ID1, ID2, SLUG, FSP-1, FN1, KRT19Case–controlCells[47]
140-5pHuman type II alveolar epithelial cells (A549)qPCR, miR-140-5p mimic/antimirCase–controlIPF=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-5pIPF and normal lung biopsy; IPF, TGF-β-stimulated and normal human lung fibroblastsArray, miR-154-5p mimic/antimirMEG3, DKK2, DIXDC1, PPP2CA, FZD 4/5/6, LRP, KREMEN1, β-CATENIN, WISP1Case–controlIPF=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-5pIPF and normal lung biopsy, IPF and normal lung fibroblastsArrayN/ACase–controlRapidly 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-5pIPF and normal lung tissues, A549 cellsArray, qPCR for 26a-5p, 30a-3p, 30b-5p, 30d-5p, 92a-3p, let-7d-5p mimic/inhibitorHMGA2, CDH2, VIM, ACTA2Case–controlIPF=10, controls=10 cells[39]
130a-3p, 142-5pBAL fluid samples; IPF and normal macrophagesqPCRN/ACase–controlIPF=9, control=7[52]
29a-3pSSc and normal skin biopsy; dermal fibroblastsqPCR, mir-29a mimicCOL1A1, TIMP1, TAB1Case–controlSSc=4–6, controls=4–6[19]
130b-3pSSc and normal skin biopsy; dermal fibroblastsqPCR, miR-130b-3p mimic/antimirCOL1A1, COL1A2, FN1, ASMACase-controlSSc=14, controls=14[58]
130b-3pIPF and normal lung biopsy; human primary type II alveolar epithelial and lung fibroblastsqPCR, miR-130b-3p mimic/antimirIGF1Case–controlIPF=4, controls=3[59]
26a-5p, let-7d-5pHuman alveolar basal epithelial cellsqPCR, miR-26a-5p mimic/antimirLIN28BCase–controlIPF=106, controls=50 (microarray data set of GSE32538)[42]
29b-3pIPF lung biopsyqPCR, miR-29b-3p mimicCOL1A1, COL3A1Case–controlIPF=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.