MicroRNAs Involved in the Lipid Metabolism and Their Possible Implications for Atherosclerosis Development and Treatment

Table 1

Overview of miR-33, miR-122, miR-27a, miR-27b, miR-144, and miR-370 functions.

MicroRNA	Target	Function	Model	Reference
miR-33/miR-33*	ABCA1	Cholesterol loading into HDL particles	THP-1, HepG2, J774, HEPA, Fu5AH, EAhy296, COS-7, and 293T cells; C57BL/6 and Ldlr^−/−mice [6] HEK293, J774, HepG2, and IMR-90 cells, C57BL/6J mice [7] HepG2, THP1, and Y1 cells; C57/BL6 mice [8] Huh7, THP1, COS7 cells; C57BL/6 mice; rhesus monkey (Macaca mulatta) [9]	[6–10]
miR33/miR-33*	NPC1	Cholesterol transport within cell from the lysosomal compartment	Huh7, THP1, COS7 cells; C57BL/6 mice; rhesus monkey (Macaca mulatta) [9]	[9]
miR-33	ABCG1	HDL formation and reverse cholesterol transport	THP-1, HepG2, J774, HEPA, Fu5AH, EAhy296, COS-7 and 293T cells; C57BL/6 and Ldlr^−/− mice [6] HEK293, Hep3B cells; Human monocyte-derived macrophages; C57BL/6J mice [10]	[6, 10]
miR-33	ABCB11, ATP8B1	Cholesterol transport from hepatocyte to biliary ducts (cholesterol retention)	HEK293 and HuH-7 cells, C57BL/6 mice; Isolated mouse hepatocytes	[11]
miR-33/miR-33*	CPT1A, CROT	Fatty acid oxidation (upregulation of miR-33/33* leads to inhibition of fatty acids oxidation)	HepG2, THP1 and Y1 cells; C57/BL6 mice [8] Huh7, THP1, COS7 cells; C57BL/6 mice; rhesus monkey (Macaca mulatta) [9]	[8, 9]
miR-33	HADBH, SIRT6, AMPKα	Fatty acid oxidation (upregulation of miR-33 leads to inhibition of fatty acids oxidation)	HepG2, THP1 and Y1 cells; C57/BL6 mice	[8]
miR-33*	SRC1, SRC3, NFYC, RIP140	Fatty acid oxidation (upregulation of miR-33* leads to inhibition of fatty acids oxidation)	Huh7, THP1, COS7 cells; C57BL/6 mice; rhesus monkey (Macaca mulatta) [9]	[9]
miR-33	IRS-2, G6PC, PCK1	Insulin signaling and glucose metabolism	Huh7, THP1, COS7 cells; C57BL/6 mice; rhesus monkey (Macaca mulatta) [9]	[9]
miR-122	–-	Anti-miR-122 introduction leads to decrease in plasmatic cholesterol	C57BL/6 mice [12] Primary hepatocytes from Balb/c mice, C57BL/6 mice [13]	[12, 13]
miR-122	SREBP and other targets	Anti-miR-122 delivery changes expression of a huge number of genes, including SREBP. This results in increase in fatty acid oxidation and decreases fatty acid and cholesterol synthesis. This results in the improvement of liver steatosis.	Primary hepatocytes from Balb/c mice, C57BL/6 mice	[13]
miR-122	MTTP, Klf6	Knockdown animals present with lower levels of circulating cholesterol and fatty acids. However, lipids accumulate in the livers (MTTP) of experimental animals leading to hepatosteatosis, fibrosis (Klf6), and tumor formation.	Mir122 conditional knockout (Mir122^loxP/loxP) mice [14] Mir122a^−/− mice; computational prediction [15]	[14, 15]
miR-27a	RXRα, ABCA1, FASN, SREBP1, SREBP2,; PPARα, PPARγ ApoA1, ApoB100, ApoE3		Huh-7.5 cells [16] HuH7, HepG2, HEK29 and HeLa cells [17]	[16, 17]
miR-27b	PPARγ, ANGPTL3, NDST1, GPAM	miR-27b is predicted to target 27 mRNAs involved in lipid metabolism; targets in the second column have already been validated.	C57BL/6J mice, Huh7 cells, computational prediction [18]	[18]
miR-27b	PPARγ, C/EBPα	Downregulation of PPARγ and C/EBPα by miR-27b leads to blockade in adipocyte differentiation.	3T3-L1, OP9 and C2C12 cells [19] 3T3-L1 cells, C57BL/6J mice [20]	[19, 20]
miR-27b	PPARα	Targeting PPARα with miR-27b affects indirectly the expression of ABCA1 and ABCG1 (PPARα targets).	3T3-L1 cells, C57BL/6J mice [20] HuH7, HepG2, HEK29 and HeLa cells [17]	[17, 20]
miR-370	CPT1A	MiR-370 affects miR-122 expression and directly targets CPT1A thus affecting fatty acid oxidation.	C57BL/6 and apoE^−/− mice [21]	[21]
miR-144	ABCA1	miR-144 expression is regulated by LXR and FXR. MiR-144 itself targets ABCA1 thus affecting cholesterol metabolism.	C57BL/6J mice [22] J774, THP-1, HepG2, Huh-7, Hepa, and EAhy926 cells; C57BL/6 mice [23]	[22, 23]

ABCA1: ATP-binding cassette A1; NPC1: Niemann-Pick disease C1; ABCG1: ATP-binding cassette G1; ABCB11: ATP-binding cassette B11; ATP8B1: ATPase class I type 8B member 1; CPT1A: carnitine palmitoyltransferase 1A; CROT: carnitine O-octaniltransferase; HADBH: hydroxyacyl-CoA-dehydrogenase; SIRT6: sirtuin-6; AMPKα: AMP-activated protein kinase subunit-α; SRC1: steroid receptor coactivator 1; SRC3: steroid receptor coactivator 3; NFYC: nuclear transcription factor Y; RIP140: receptor-interacting protein 140; IRS-2: insulin receptor substrate 2; G6PC: glucose-6-phosphatase; PCK1: phosphoenolpyruvate carboxykinase; SREBP: sterol regulatory element-binding protein; MTTP: microsomal triglyceride transfer protein; Klf6: Kruppel-like factor 6; RXRα: retinoid X receptor α; FASN: fatty acid synthase; PPARα: peroxisome proliferator-activated receptor α; PPARγ: peroxisome proliferator-activated receptor γ; ApoA1: apolipoprotein A1; ApoB100: apolipoprotein B100; ApoE3: apolipoprotein E3; ANGPTL3: angiopoietin-like 3; NDST1: N-deacetylase-N-sulfotransferase 1; GPAM: glycerol-3-phosphate acyltransferase; C/EBPα: CCAAT/enhancer-binding protein α.