MiR-33 contributes to the regulation of cholesterol homeostasis.
Cholesterol metabolism is tightly regulated at the cellular level. Here we show that miR-33, an intronic microRNA (miRNA) located within the gene encoding sterol-regulatory element-binding factor-2 (SREBF-2), a transcriptional regulator of cholesterol synthesis, modulates the expression of genes involved in cellular cholesterol transport. In mouse and human cells, miR-33 inhibits the expression of the adenosine triphosphate-binding cassette (ABC) transporter, ABCA1, thereby attenuating cholesterol efflux to apolipoprotein A1. In mouse macrophages, miR-33 also targets ABCG1, reducing cholesterol efflux to nascent high-density lipoprotein (HDL). Lentiviral delivery of miR-33 to mice represses ABCA1 expression in the liver, reducing circulating HDL levels. Conversely, silencing of miR-33 in vivo increases hepatic expression of ABCA1 and plasma HDL levels. Thus, miR-33 appears to regulate both HDL biogenesis in the liver and cellular cholesterol efflux.
Rayner
Katey J
KJ
Department of Medicine, Leon H. Charney Division of Cardiology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY 10016, USA.
Suárez
Yajaira
Y
Dávalos
Alberto
A
Parathath
Saj
S
Fitzgerald
Michael L
ML
Tamehiro
Norimasa
N
Fisher
Edward A
EA
Moore
Kathryn J
KJ
Fernández-Hernando
Carlos
C
D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077296:Niemann-Pick C1 Protein; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
C577836:ABCA1 protein, human; C487540:ABCG1 protein, mouse; C505693:APOA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D047908:Intracellular Signaling Peptides and Proteins; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D011506:Proteins; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol
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