Role of microRNAs in alcohol-induced liver disorders and non-alcoholic fatty liver disease

Table 1 MicroRNA targets involved in alcoholic liver disease pathogenesis

miRNA	Source of sample	miRNA target
let-7[27]	Animal models	Lin28, HMGA2
	Human HSCs
miR-19b[28]	Animal models	TGFβRII, Col1α2, MeCP2
	Human HSCs
miR-21[36,37]	Animal models	FASLG, DR5, Crebl2
miR-26a[35]	Animal models	DUSP4, DUSP5
miR-27a[44,52]	Animal models	Sprouty2, CD206
	HMC
	Humans (plasma)
miR-34a[29,43]	Animal models	SIRT1, CASP2
	Human HSCs
	NHH
	HiBECs
	Humans (liver biopsy)
miR-103 and miR-107[53]	Humans (liver biopsy)	Caveolin-1
miR-122[32,124,125]	Animal models	P4HA1, HO-1, Cyclin G1, Bcl-w, HIF-1α
miR-155[38,39,97,126,127]	Animal models	TNFα, SHIP1, SOCS1, IRAKM, C/EBPβ
miR-181b-3p[40]	Animal models	Importin α1
miR-182[30]	Animal models	SLC1A1, Cofilin 1, CCL20, CXCL1, IL-8, Cyclin D1, IL-6
	Humans (serum samples and liver biopsy)
miR-199[128]	Animal models	ET-1, ET-BR
miR-200a[31]	Animal models	ZEB-2
miR-212[46]	Caco-2 cells	ZO-1
	Humans (colon biopsy)
miR-214[24,34]	Animal models	POR, GSR, CYP2E1
	HHCs
miR-217[41]	Animal models	SIRT-1
miR-223[45]	Animal models	p47phox, IL-6
	Humans (serum)
miR-291b[42]	Animal models	Tollip
	HPBMs
miR-378[59]	Animal models	Gli-3
miR-497[25]	Animal models	Btg2, Yy1

HSCs: Hepatic stellate cells; HMGA2: High mobility group AT-hook 2; TGFβRII: Transforming growth factor β receptor II; Col1α2: Collagen type I α 2 chain; MeCP2: Methyl-CpG binding protein 2; FASLG: Fas ligand; DR5: Death receptor 5; Crebl2: cAMP responsive element binding protein like 2; DUSP: Dual specificity phosphatase; HMC: Human Monocyte Cells; NHH: Normal Human Hepatocytes; HiBECs: Human intrahepatic Biliary Epithelial Cells; SIRT1: sirtuin 1; CASP2: caspase 2; P4HA1: prolyl 4-hydroxylase subunit α 1; HO-1: heme oxygenase-1; BCL-W: Bcl-2-like protein 2; HIF-1α: Hypoxia inducible factor 1 α; TNFα: Tumor necrosis factor α; SHIP1: Src homology 2 domain-containing inositol phosphatase 1; SOCS1: Suppressor of cytokine signaling 1; IRAKM: Interleukin 1 receptor associated kinase 3; C/EBPβ: CCAAT/enhancer binding protein β; SLC1A1: Solute carrier family 1 member 1; CCL20: C-C motif chemokine ligand 20; CXCL1: C-X-C motif chemokine ligand 1; IL: Interleukin; ET-1: Endothelin-1; ET-BR: Endothelin-B receptor; ZEB-2: Zinc finger E-box binding homeobox 2; ZO-1: Zonula occludens 1; HHCs: Human Hepatoma Cells; POR: Cytochrome P450 oxidoreductase; GSR: Glutathione reductase; CYP2E1: Cytochrome P450 2E1; p47phox: Neutrophil cytosolic factor 1-like; HPBMs: Human Peripheral Blood Monocytes; Tollip: Toll interacting protein; Gli3: GLI Family Zinc Finger 3; Btg2: B-cell translocation gene 2; YY1: Yin yang 1; miRNA: MicroRNA.

Table 2 Summary of microRNAs associated with non-alcoholic fatty liver disease

miRNA	Source of samples	Change	Main targets
miR-9[129]	Human serum;	Upregulated	Onecut2; SIRT1
	Human hepatocyte cell line
miR-10b[130]	Human hepatocyte cell line	Downregulated	PPARα
miR-15b[131,132]	Animal models	Upregulated
	Human serum
miR-16[104]	Human serum	Upregulated
miR-17[74]	Human liver	Downregulated
miR-19[84]	Human serum	Upregulated
miR-21[86,87,99,133-136]	Animal models	Upregulated	PPARα; TGF-β
	Human hepatocyte cell line		PTEN
	Human liver and serum
miR-21[85,89,137,138]	Animal models	Downregulated	HMGCR; FABP7
	Human liver
	Human hepatocyte cell line
miR-24[139]	Animal models	Upregulated	Insig1; SREBP
	Human hepatocyte cell line
miR-26[140]	Animal models	Downregulated	IL-6, IL-7
miR-27a[141]	Animal models	Downregulated
miR-27b[102]	Human serum	Upregulated
miR-29a[142,143]	Animal models	Downregulated	HMGCR; LPL
miR-29c[85,89,90]	Animal models	Downregulated	DNMT3A; DNMT3B
miR-30b[83]	Human liver	Downregulated	ITGAX; FABP4
	Human hepatocyte cell line
miR-30c[144]	Human serum	Upregulated
miR-31[74,89]	Human liver	Upregulated
	Animal models
miR-33a[73,76]	Human liver	Upregulated	ABCA1; ABCA2
miR-33a[85]	Human liver	Downregulated
MiR-34a[71,81,82,85,87,89,90,92,104,105,145-148]	Animal models	Upregulated	SIRT1; HNF4α; PPARα
	Human hepatocyte cell line
	Human liver and serum
miR-99a[149]	Human serum	Downregulated
miR-101[150]	Human hepatocyte cell line	Upregulated	ABCA1
	Human monocyte cell line
miR-103[53,89,151]	Animal models	Upregulated	Cav1
	Human liver and serum
miR-103a[152]	Human liver	Upregulated
	Human hepatocyte cell line
miR-106b[152]	Human liver	Upregulated
miR-107[53,89]	Animal models	Upregulated	Cav1
	Human liver
miR-122[81,84,86,87,101-104,106,153]	Animal models	Upregulated
	Human Serum
miR-122[71,82-85,89,90,99,106,141,154,155]	Animal models	Downregulated	ACC-2; HAMP; FAS; HMGCR; SREBF-1c
	Human liver		SREPBF-2; HIF-1α; Vimentin; MAP3K3
miR-125b[84]	Human serum	Upregulated
miR-125b[156]	Animal models	Downregulated	FAS
miR-139-5p[83]	Human liver	Downregulated	TNFα
miR-144[76]	Human Liver	Upregulated	ABCA1
miR-144[157]	Animal models	Downregulated	TLR-2
miR-146a[158]	Animal models	Upregulated
	Human hepatocyte cell line
miR-146a[132]	Animal models	Downregulated	Wnt1; Wnt5
	Human hepatocyte cell line
Mir-146b[149,159]	Animal models	Downregulated	IRAK1
	Human serum		TRAF6
	Human hepatocyte cell line
miR-146b[71,83,158]	Animal models	Upregulated
	Human liver
	Human hepatocyte cell line
miR-149[160]	Animal models	Upregulated	FGF-21
	Human hepatocyte cell line
miR-150[74]	Human liver	Upregulated
miR-152[158]	Animal models	Upregulated
	Human hepatocyte cell line
miR-155[90,97-99,161,162]	Animal models	Upregulated	SOCS1; C/EBP-Β; CES3; PDGF; SMAD3
	Human hepatocyte cell line
miR-155[96]	Animal models	Downregulated	LXRα
	Human liver and serum
miR-181a[82]	Animal models	Upregulated
miR-181d[149]	Human serum	Downregulated
miR-182[74]	Human liver	Upregulated	FOXO3
miR-183[74]	Human liver	Upregulated
miR-192[84,90]	Animal models	Downregulated
	Human liver
miR-192-5p[82,84,86,102,106]	Animal models	Upregulated
	Human liver and serum
miR-194[89]	Animal models	Upregulated
miR-197[149]	Human serum	Downregulated
miR-199[163]	Animal models	Upregulated	Cav1; PPARα
	Human hepatocyte cell line
	Human liver
miR-200a/b/c[74,82,89,90,141,158,162,164]	Animal models	Upregulated	ZEB1; CDH1; EZH2; IRP1
	Human hepatocyte cell line
miR-203[90,132]	Animal models	Downregulated
miR-212[165]	Animal models	Upregulated	FGF-21
	Human hepatocyte cell line
miR-214[71,166]	Human liver	Upregulated
	Animal models
miR-216[167]	Animal models	Downregulated
miR-219a[74]	Human liver	Downregulated
miR-221[73]	Human liver	Downregulated
miR-221[89,90,99]	Animal models	Upregulated
miR-222[99]	Animal models	Upregulated
miR-223[86,164]	Animals models	Upregulated	IRP1
	Human serum
miR-224[73,74]	Human liver	Upregulated
miR-291b[168]	Animal models	Upregulated	AMPKα1
miR-302a[167]	Animals model	Downregulated	ELOVL6
miR-331[144]	Human serum	Upregulated
miR-335[89]	Animal models	Upregulated
miR-375[84]	Human serum	Upregulated
miR-378i[74]	Human liver	Downregulated
miR-421[169]	Animal models	Upregulated	SIRT-3
miR-422a[83]	Human liver	Downregulated
miR-429[141]	Animal models	Upregulated
miR-451[87]	Human Serum	Upregulated
miR-451[89,141,170]	Animal models	Downregulated	AMPK/AKT
	Human liver
miR-467b[171]	Animal models	Downregulated	LPL
miR-576[152]	Human liver	Downregulated	RAC1
	Human hepatocyte cell line
miR-590[74]	Human liver	Downregulated
miR-892a[152]	Human liver	Upregulated
	Human hepatocyte cell line
miR-1290[102]	Human serum	Upregulated

Onecut2: One cut homeobox 2; SIRT: Sirtuin; PPARα: Peroxisome proliferator activated receptor α; TGF-β: Transforming growth factor β; PTEN: Phosphatase and tensin homolog; HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase; FABP: Fatty acid binding protein; Insig1: Insulin induced gene 1; SREBP: Sterol regulatory element binding protein; IL: Interleukin; LPL: Lipoprotein lipase; DNMT: DNA methyltransferase; ITGAX: Integrin subunit α X; ABCA: ATP binding cassette subfamily A; HNF4α: Hepatocyte nuclear factor 4 α; Cav1: Caveolin 1; ACC-2: Acetyl-CoA carboxylase 2; SREBF: Sterol regulatory element binding transcription factor; HIF-1α: Hypoxia inducible factor 1 α; MAP3K3: Mitogen-activated protein kinase kinase kinase 3; FAS: Fatty acid synthase; TNFα: Tumour necrosis factor α; TLR-2: Toll-like receptor 2; Wnt: Wnt family member; IRAK1: Interleukin 1 receptor associated kinase 1; TRAF6: TNF receptor associated factor 6; FGF-21: Fibroblast growth factor 21; SOCS1: Suppressor of cytokine signaling 1; C/EBPβ: CCAAT/enhancer binding protein β; CES3: Carboxylesterase 3; PDGF: Platelet derived growth factor; SMAD3: SMAD family member 3; LXRα: Liver X receptor; FOXO3: Forkhead box O3; ZEB-1: Zinc finger E-box binding homeobox 1; CDH1: Cadherin 1; EZH2: Enhancer of zeste 2 polycomb repressive complex 2; IRP1: Iron regulatory protein 1; AMPKα1: AMPK: Adenosine monophosphate activated protein kinase α 1; ELOVL6: ELOVL fatty acid elongase 6; AMPK: Adenosine monophosphate activated protein kinase; AKT: AKT serine/threonine kinase 1; RAC1: Ras-related C3 botulinum toxin substrate 1.