Role of noncoding RNAs in liver fibrosis

Table 1 Noncoding RNAs in the pathogenesis and progression of liver fibrosis

ncRNAs	Target genes	Signaling pathways	Ref.
miR-199a-3p	CAV2	TGF-β/Smad	[20]
miR-497	Smad7	TGF-β/Smad	[17]
miR-21	Smad2/3/7	TGF-β/Smad	[15]
	TGF-β	PI3K/AKT	[25]
	-	PPARα	[51]
	-	PDCD4/AP-1	[51,52]
	-	Smad7/Smad2/3/NOX4, Spry1/ERK/NF-κB	[51,53]
	-	HIF-1α/VEGF	[54]
miR-16	Smad2, Wnt3a	TGF-β/Smad, Wnt	[18]
miR-130a-3p	TGF-βRI, TGF-βRII; MAPK1	TGF-β; MAPK	[22]
miR-98-5p	TGF-βRI	TGF-β1/Smad3	[19]
miR-6133-5p	TGF-βRII, FGFRI	TGF-β/Smad2/3, AKT/ERK/JNK	[55]
miR-708	ZEB1	Wnt/β-catenin	[29]
exo-miR-1297	PTEN	PI3K/AKT	[26]
miR-350	SPRY2	PI3K/AKT and ERK	[56]
miR-34c	ACSL1	-	[57]
miR-200c	HAS2	-	[58]
miR-451, miR-185	EphB2	-	[42]
miR-20b-5p	STAT3	STAT3	[97]
lncRNA SNHG7	miR-29b, DNMT3A	Autophagy pathway	[40]
lncRNA PVT1	miR-152, ATG14	Autophagy pathway	[39]
lncRNA SCARNA10	PRC2	TGF-β	[23]
lncRNA LOC102551149	miR-23a-5p, PTEN	PI3K/AKT/mTOR/Snail	[27]
lncRNA MALAT1	-	Wnt/β-catenin	[31]
lncRNA NEAT1	miR-139-5p, β-catenin	β-catenin/SOX9/TGF-β1	[30]
	miR-129-5p, PEG3	NF-κB	[32]
	miR-129-5p, SOCS2	-	[33]
	miR-148a-3p, miR-22-3p, Cyth3	-	[34]
lncRNA Lfar1	-	NF-κB	[35]
lncRNA GAS5	miR-433-3p, TLR10	NF-κB	[36]
lncRNA-ROR	miR-6499-3p	NF-κB	[99]
lncRNA Airn	EZH2	KLF2-eNOS-sGC	[98]
lncRNA MEG3	NLRC5	-	[37]
lncRNA NORAD	miR-495-3p, S1PR3	-	[60]
lncRNA XIST	miR-539-3p, ADAMTS5	-	[44]
lncRNA Mical2	miR-203a-3p, p66Shc	-	[43]
circRNA608	miR222, PINK1	Autophagy pathway	[41]
circMTO1	miR-17-5p, Smad7	-	[24]
circFBXW4	miR-18b-3p, FBXW7	-	[48]
circCREBBP	miR-1291, LEFTY2	-	[49]
circ_0071410	miR-9-5p	-	[50]
circUbe2k	miR-149-5p, TGF-β2	-	[59]

ncRNAs: Noncoding RNAs; CAV2: Caveolin-2; TGF-β: Transforming growth factor-β; PI3K: Phosphatidylinositol 3-kinase; AKT: Serine/threonine kinase 1; PPAR: Peroxisome proliferator-activated receptor; PDCD4: Programmed cell death protein 4; AP-1: Activation protein-1; NOX4: Nicotinamide adenine dinucleotide phosphate oxidase 4; Spry1: Sprouty 1; ERK: Extracellular regulated kinase; NF-κB: Nuclear factor κ light chain enhancer of activated B cells; HIF-1α: Hypoxia-inducible factor-1α; VEGF: Vascular endothelial growth factor; TGF-βRI: TGF-β type I receptor; MAPK: Mitogen-activated protein kinase; FGFR: Fibroblast growth factor receptor; JNK: c-Jun N-terminal kinase; ZEB1: Zinc finger E-box binding homeobox 1; PTEN: Phosphatase and tensin homology deleted on chromosome ten; ACSL1: Acyl-CoA synthetase long chain family member 1; HAS2: Hyaluronic acid synthase; EphB2: Erythropoietin-producing hepatocellular receptor B2; SNHG7: Small nucleolar RNA host gene 7; DNMT3A: DNA methyltransferase 3 alpha; PVT1: Plasmacytoma variant translocation 1; ATG: Autophagy-related gene; SCARNA10: Small Cajal body-specific RNA 10; PRC2: Polycomb repressive complex 2; mTOR: Mammalian target of rapamycin; MALAT1: Metastasis-associated lung adenocarcinoma transcript1; NEAT1: Nuclear enriched abundant transcript1; SOX9: SRY-related high mobility group-box gene9; PEG3: Paternally expressed gene 3; SOCS2: Suppressor of cytokine signaling 2; Cyth3: Cytohesin 3; Lfar1: Liver fibrosis associated lncRNA1; GAS5: Growth arrest-special transcript 5; TLR: Toll-like receptor; MEG3: Materally expressed gene 3; NLRC5: NLR Family CARD Domain Containing 5; NORAD: Non-coding RNA activated by DNA damage; S1PR3: Sphingosine 1-phosphate receptor 3; XIST: X-inactive-specific transcript; ADAMTS5: ADAM metallopeptidase with thrombospondin type 1 motif 5; Mical2: Molecule interacting with CasL2; Shc: Src homologous-collagen homologue; PINK1: PTEN-induced putative kinase 1; MTO1: Mitochondrial tRNA translation optimization 1; FBXW4: F-box and WD repeat domain containing 4; CREBBP: CREB binding protein; LEFTY2: Left-right determinant cluster 2; Ube2k:Ubiquitin conjugating enzyme E2 K; STAT3: Signal transducer and activator of transcription 3; Airn: Antisense Igf2r RNA; ROR: Regulator of reprogramming; EZH2: Enhancer of zeste homolog 2; KLF2: Krüppel-like transcription factor 2; eNOS: Endothelial nitric oxide synthase; sGC: Soluble guanylate cyclase.

Table 2 Noncoding RNAs for the potential treatment of liver fibrosis

ncRNAs	Target genes	Signaling pathways	Ref.
miR-29a	PI3KP85α	PI3K/AKT	[79]
	Fstl	TGF-β/Smad2, JNK	[21]
miR-223	NLRP3 inflammasome	NOD signaling pathway	[81]
	GLI2, PDGFRα/β	Hedgehog, PDGF	[82]
hB-MSCs-derived exo-miR-618	Smad4	TGF-β/Smad2	[87]
3DhESCs-derived exo-miR-6766-3p	TGFβRII	TGF-β/Smad	[89]
hT-MSCs-derived exo-miR-486	Smo	Hedgehog/GlI2	[88]
NK cells-derived exo-miR-223	ATG7	Autophagy pathway	[85]
KCs-derived exo-miR-690	NADK	-	[84]
lncRNA SNHG	miR-15a, MURF1	UVRAG/ATG5/Wnt5a	[93]
lncRNA BIHAA1	miR-667-5p	-	[92]
MSCs-derived exo-circDIDO1	miR-141-3p	PTEN/AKT	[73]
MSCs-derived exo-circCDK13	miR-17-5p, KAT2B	PI3K/AKT, NF-κB	[94]

ncRNAs: Noncoding RNAs; PI3K: Phosphatidylinositol 3-kinase; AKT: Serine/threonine kinase 1; Fstl: Follistatin-like 1; TGF-β: Transforming growth factor-β; JNK: c-Jun N-terminal kinase; NLRP3: NOD-like receptor family, pyrin domain containing 3; Smo: Smoothened; GLI2: Gliotactin family zinc finger 2; PDGFR: Platelet-derived growth factor receptor; MSC: Mesenchymal stem cell; hB-MSC: Human bone MSC; hT-MSC: Human tonsil-derived MSC; 3DhESC: 3D-cultured human embryonic stem cells; TGF-βRII: TGF-β type II receptor; ATG: Autophagy-related gene; KCs: Kupffer cells; NADK: NAD kinase; SNHG: Small nucleolar RNA host gene; SMURF1: Smad ubiquitin regulatory factor 1; UVRAG: UV radiation resistance associated gene; DIDO1: Death inducer-obliterator 1; PTEN: Phosphatase and tensin homology deleted on chromosome ten; CDK13: Cyclin dependent kinase 13; KAT2B: K (lysine) acetyltransferase 2B.