| First Author | Rayner KJ | Year | 2010 |
| Journal | Science | Volume | 328 |
| Issue | 5985 | Pages | 1570-3 |
| PubMed ID | 20466885 | Mgi Jnum | J:160971 |
| Mgi Id | MGI:4456894 | Doi | 10.1126/science.1189862 |
| Citation | Rayner KJ, et al. (2010) MiR-33 contributes to the regulation of cholesterol homeostasis. Science 328(5985):1570-3 |
| abstractText | 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. |
