Table 1.

ncRNAs contributing to cardiac fibrosis.

Non-coding RNAs	Effect (s)	Expression in CF	Targets	Signaling pathway	Model	References
miRNA
miR-21	Profibrosis	Upregulated	Spry1, PTEN CADM1	↑TGF-β1 → ↓PTEN → ↑MMP-2 CADM1/STAT3 pathway ↑cardiac fibrosis	Rat CFs	(51, 52)
miR-26a/b	Profibrosis	Upregulated	TRPC3	↑MiR-26a → ↓ TRPC3 → ↑CF	Dog fibroblasts model	(53)
			Col1a2/CTGF	miR-26b-5p → ↓Col1a2/CTGF → ↑CF	Mouse CFs	(54)
miR-34	Profibrosis	Upregulated	VEGF, neurogenic locus notch homolog protein 1, vinculin, PPP1R10	Contributing to cardiomyocyte aging; inhibiting miR-34 and limiting cardiac fibrotic events	MI and TAC mice	(19, 55)
miR-132	Antifibrosis	Downregulated	Ras/Rap/SynGAP; methyl-CpG-binding protein 2	Akt/eNOS/Bcl-2 signaling pathway ↓Ras/Rap GTPase-activating protein ↓SynGAP;methyl-CpG-binding domain protein 2 → ↓CF	MI -CD1 mice	(56)
miR-133/miR-30	Antifibrosis	Downregulated	CTGF	Contributing to the progress of fibrosis via connective tissue growth factor targeting	Renin-2 tg rat	(57)
miR-133a	Antifibrosis	Downregulated	Collagen α-1(I) chain	Transgenic overexpression in cardiomyocytes inhibits fibrotic progress across overload of pressure and diabetic cardiomyopathy	TAC mice	(58)
miR-155	Profibrosis	Upregulated	Son of seven less gene (Sos1)	Macrophage-derived mir-155–comprising exosomes suppressing proliferation Of Fibroblasts and enhancing inflammation of fibroblasts across cardiac injury	mir-155–deficient mice	(59)
miR-199b	Antifibrosis	Downregulated	Dyrk1a calcineurin/NFAT target gene	Nuclear kinase Dyrk1a is targeted by miRNA-199b in an auto-amplification loop enhancing calcineurin/NFAT signaling inhibition → ↓CF	mouse and human heart failure	(60)
miR-208	Profibrosis	Upregulated	Myosin-6, myosin-7	Inhibition results in decreased progress of fibrosis subject to cardiac stress	miR-208 mutant animals	(61)
miR-214	Antifibrosis	Downregulated	Sodium/calcium exchanger (1Ncx1)	Inhibition results in excessive progress of cardiac fibrosis following myocardial infarction	Ischemic cardiac tissue	(62)
miR-455	Antifibrosis	Downregulated	collagen I and III CTGF	miR-455 → ↓ collagen I and III /CTGF ↓CF	Male diabetic mice	(63)
miRNA-155	Profibrosis	Upregulated	Ski SnoN	↓Antifibrotic Sloan–Kettering Institute proto-oncogene (Ski)/Ski-associated new gene, non–Alu-comprising (SnoN) signaling (negative TGF-β signaling regulating factors) → ↑CF	Diabetic (db/db) mice	(13)
miR−223	Profibrosis	Upregulated	RASA1(RAS p21 protein activator 1)	siRASA1 enhanced MEK1/2, ERK1/2 and AKT phosphorylation → ↑ collagen I, collagen III, and α-SMA → ↑CF	CFs	(64)
miR-9	Antifibrosis	Downregulated	TGFBR2	Suppressing TGF-β receptor II → ↓CF	High glucose/human CFs	(65)
Let-7i	Antifibrosis	Downregulated	IL-6 Mac-2	Let-7i → ↓ interleukin-6/collagens → ↓CF	AngII/mouse; NRCFs	(66)
Let-7c	Antifibrosis	Downregulated	Activate Oct4 and Sox2	Improvement in cardiac function ↓apoptosis, ↓fibrosis, ↓number of discoidin domain receptor 2–positive fibroblasts	MI/mouse; NRCFs	(67)
lncRNAs
lncRNA H19	Profibrosis	Upregulated	ERK1/2, Dual-specificity phosphatase 5 (DUSP5)	↑H19 → ↓DUSP5 (negative regulation of prohypertrophic signaling by↓ ERK1/2) → ↑α-SMA↑/cardiac fibroblast proliferation	Isolated rat cardiac fibroblasts	(68)
			miR-455 CTGF, collagen I, III, α-SMA	H19 and miR-455 modulated myocardial extracellular matrix accumulation	Male diabetic mice	(63)
lncRNA MIAT	Profibrosis	Upregulated	miRNAs-29, 21, 133, 30, and 24	MIAT↑ → miR-24↓ → Furin/TGF-β1↑ → cardiac fibrotic event↑	Anesthesia of healthy male C57BL/6 mice was carried out with Avertin (160 mg/kg, i.p. Sigma–Aldrich)	(69)
Malat1	Profibrosis	Upregulated	miR-145	↑MALAT1 → ↓miRNA-145 (miR-145) → ↑ TGF-β1 → ↑CF	MI mouse heart and AngII-treated CFs	(70)
			Mir-24 Mir-29 Mir-30 Mir-133	↑MALAT1 → ↓ miR-24 → ↑ Furin and ↑TGF-β1 → ↑CF	Mouse model of MI	(69, 71)
Meg3	Profibrosis	Upregulated	p53 signaling MMP-2	Blockage of inducing Mmp-2 expression through TGF r-βI took place with Meg3 silencing by inhibiting P53 binding on the Mmp-2promoter	In vivo In vitro	(72)
lncRNA SRA1	Profibrosis	Upregulated	miR-148b	lncRNA SRA1 → ↓ miR-148b → ↑CF	Rat model	(73)
Wisper	Antifibrosis	Upregulated	Splicing of Plod2 mRNA by enabling nuclear localization of TIAR	Regulates cardiac fibrosis after injury ↓Pathological progress of cardiac fibrosis in response to MI while preventing unfavorable remodeling	Murine model of MI	(74)
AK081284	Profibrosis	Upregulated	TGF-β1	IL-17/AK081284/TGF-β1 signaling pathways mediate collagen production → ↑CF induced by high glucose	Diabetic mouse Myocardial fibrosis model	(75)
lncRNA-NR024118 and Cdkn1c	Antifibrosis	Proregulated	↓cell cycle ↓ Cdkn1c	↑ AngII → blocking AT1 receptor → ↓NR024118 → ↑CF	AngII/adult rat CFs	(75, 76)
lncRNA PFL (NONMMUT02255)	Profibrosis	Upregulated	let-7d Ptafr	lncRNA PFL → ↓ let-7d → Ptafr → ↑CF	MI mice cardiac fibrosis in mice	(77, 78)
lncRNA-NONMMUT022554	Profibrosis	Upregulated	ECM–receptor PI3K-Akt	May affect ECM-receptor interactions and the phosphoinositid-3 kinase/protein kinase B (PI3K-Akt) signaling pathway → ↑CF	MI/mouse	(79)
Mhrt	Antifibrosis	Downregulated	Brg1—chromatin remodeling	Binding of Mhrt to the helicase domain of Brg1, a domain which seems critical for tethering Brg1 to chromatin zed DNA targets	Pressure-overloaded hearts by trans aortic constriction	(80)
Circular RNAs
CircActa2	Profibrosis	Upregulated	miR-548f-5p. NRG-1	NRG-1/circACTA2/miR-548f-5p Axis.	Animal model of cardiac remodeling and heart failure	(81, 82)
circAmotl1	Antifibrosis	Downregulation	AKT1/PDK1	↓Dox/↑resistant fibrosis cardiac repair	Cardiac fibroblasts	(83)
circRNA_010567	Profibrosis	Upregulation	↓ miR-141 TGF-β1	CircRNA_010567 → ↓miR-141 → ↑TGF-β1 → ↑Col I, Col III and α-SMA → ↑CF	Mice myocardial fibrosis models	(84)