MiR-33 Contributes to the Regulation of Cholesterol Homeostasis

Overview

Journal Science

Specialty Science

Date 2010 May 15

PMID 20466885

Citations 627

Authors

Katey J Rayner

Yajaira Suarez

Alberto Davalos

Saj Parathath

Michael L Fitzgerald

Norimasa Tamehiro

Edward A Fisher

Kathryn J Moore

Carlos Fernandez-Hernando

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

MiR-33 as a novel diagnostic biomarker for distinguishing cholesterol from adenomatous polyps: a case-control study.

Hu X, Zhang P, Wang T, Li Q, Li M, Zhao Z Hereditas. 2025; 162(1):37.

PMID: 40087680 DOI: 10.1186/s41065-025-00407-6.

Cellular Phenotypic Transformation During Atherosclerosis: The Potential Role of miRNAs as Biomarkers.

Wassaifi S, Kaeffer B, Zarrouk S Int J Mol Sci. 2025; 26(5).

PMID: 40076710 PMC: 11900927. DOI: 10.3390/ijms26052083.

Inhibiting MiR-33a-3p Expression Fails to Enhance ApoAI-Mediated Cholesterol Efflux in Pro-Inflammatory Endothelial Cells.

Huang K, Pokhrel A, Echesabal-Chen J, Scott J, Bruce T, Jo H Medicina (Kaunas). 2025; 61(2).

PMID: 40005445 PMC: 11857470. DOI: 10.3390/medicina61020329.

The Role of MicroRNAs in Liver Functioning: from Biogenesis to Therapeutic Approaches (Review).

Kozlov D, Rodimova S, Kuznetsova D Sovrem Tekhnologii Med. 2025; 15(5):54-79.

PMID: 39967915 PMC: 11832066. DOI: 10.17691/stm2023.15.5.06.

Epigenetic regulation in coronary artery disease: from mechanisms to emerging therapies.

Gao R, Liu M, Yang H, Shen Y, Xia N Front Mol Biosci. 2025; 12:1548355.

PMID: 39959304 PMC: 11825346. DOI: 10.3389/fmolb.2025.1548355.

References

Wellington C, Walker E, Suarez A, Kwok A, Bissada N, Singaraja R . ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation. Lab Invest. 2002; 82(3):273-83. DOI: 10.1038/labinvest.3780421. View

Krutzfeldt J, Rajewsky N, Braich R, Rajeev K, Tuschl T, Manoharan M . Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005; 438(7068):685-9. DOI: 10.1038/nature04303. View

Krieger M . Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest. 2001; 108(6):793-7. PMC: 200944. DOI: 10.1172/JCI14011. View

Oram J, Vaughan A . ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr Opin Lipidol. 2000; 11(3):253-60. DOI: 10.1097/00041433-200006000-00005. View

Brooks-Wilson A, Marcil M, Clee S, Zhang L, Roomp K, Van Dam M . Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet. 1999; 22(4):336-45. DOI: 10.1038/11905. View

Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S . LNA-mediated microRNA silencing in non-human primates. Nature. 2008; 452(7189):896-9. DOI: 10.1038/nature06783. View

Tall A, Yvan-Charvet L, Terasaka N, Pagler T, Wang N . HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis. Cell Metab. 2008; 7(5):365-75. DOI: 10.1016/j.cmet.2008.03.001. View

Bodzioch M, Orso E, Klucken J, Langmann T, Bottcher A, Diederich W . The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease. Nat Genet. 1999; 22(4):347-51. DOI: 10.1038/11914. View

Horton J, Goldstein J, Brown M . SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002; 109(9):1125-31. PMC: 150968. DOI: 10.1172/JCI15593. View

10.

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

11.

Esau C, Davis S, Murray S, Yu X, Pandey S, Pear M . miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006; 3(2):87-98. DOI: 10.1016/j.cmet.2006.01.005. View

12.

Ory D . The niemann-pick disease genes; regulators of cellular cholesterol homeostasis. Trends Cardiovasc Med. 2004; 14(2):66-72. DOI: 10.1016/j.tcm.2003.12.003. View

13.

Beaven S, Tontonoz P . Nuclear receptors in lipid metabolism: targeting the heart of dyslipidemia. Annu Rev Med. 2006; 57:313-29. DOI: 10.1146/annurev.med.57.121304.131428. View

14.

Rust S, ROSIER M, Funke H, Real J, Amoura Z, Piette J . Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1. Nat Genet. 1999; 22(4):352-5. DOI: 10.1038/11921. View