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.